Superoxide dismutase activity in colostrum, transitional and mature human milk

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3rd-5th days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation.     

Psychodermatology: a brief review for clinicians

Psychodermatologic disorders are conditions involving an interaction between the mind and the skin. These disorders fall into three major categories: psychosomatic disorders, primary psychiatric disorders and secondary psychiatric disorders (Koo 1995). The treatment of psychodermatologic disorders is almost impossible without a holistic team approach involving psychiatrist, dermatologist and psychologist. Majority of psychodermatologic disorders can be treated with cognitive-bihevioral psychotherapy, psychoterapeutic stress-and-anxiety-management techniques and psychotropic drugs. Psychopharmacologic treatment with anxiolytics, antidepressants, antipsychotics and mood stabilizers can be prescribed by dermatologist, after consulting the psychiatrist.     

Acquired factor V inhibitors in a polytraumatized patient

BACKGROUND: Factor V (FV) inhibitors are a rare disorder reported for the first time about fifty years ago, mostly with the unknown cause. The appearance of FV inhibitors is usually preceded by surgery, infections, administration of antibiotics or transfusions. Clinical manifestations of the presence of FV inhibitors vary from mild to severe and in some instances fatal hemorrhage. CASE REPORT: A healthy 51-year-old man with severe multiple injuries (traffic accident), and hemorrhage, which ocurred during the orthopedic treatment, was admitted with hemoptysis, epistaxis and hematoma of the right upper leg, and with prolonged prothrombin time (PT), and activated partial thromboplastin time (aPTT). Treatment with vitamin K, fresh-frozen plasma and cryoprecipitate stopped the hemorrhage, but the results of coagulation tests were not normalized. The correction of aPTT and PT with normal plasma showed the decreased activity of FV (1%) due to the presence of inhibitors (titer 17.5 IU). The abnormal resuts of coagulation tests remained for three weeks, but without clinically manifested hemorrhagic syndrome. At the fourth week after the appearance of FV inhibitors PT, aPTT and the activity of FV became normal and antibodies disappeared spontaneously. CONCLUSION: Our patient with polytrauma developed a mild hemorrhagic syndrome due to the presence of FV inhibitors five weeks after the accident. Hemorrhage was treated with substitution therapy. The cause of the development of FV inhibitors was unclear ("fibrin glue" was not used during the orthopedic treatment). Factor V inhibitors disappeared spontaneously within four weeks. The fast spontaneous disappearance of FV inhibitors in our patient, confirmed the observations of some authors that they disappeared faster in those patients who were surgically treated prior to their appearance.     

Quantitative analysis of the nephron during human fetal kidney development

BACKGROUND: The development of human kidney is a complex process. The number, shape, size, and distribution of nephrons as functional units in a kidney, provide some important information about the organization of the kidney. The aim of this study was to extend the knowledge of the developing human kidney by studying nephrons in the kidney's cortex during gestation. METHODS: Kidney tissue specimens of 32 human fetuses, the gestational age from IV lunar month (LM IV) to LM X, were analysed. Specimens were divided in ten groups based on gestational age. Stereological methods were used at the light microscopic level to estimate the volume densities of the corpuscular and tubular components of the nephron in the cortex of the developing human kidney. RESULTS: Nephron polymorphism was the main characteristic of the human fetal kidney during development. In younger fetuses, just below the renal capsule, there was a wide nephrogenic zone. It contained the condensed mesenchyme and terminal ends of the ureteric bud. Nephrons, in the different stages of development, were located around the ureteric bud which branched in the cortical nephrogenic zone and induced nephrogenesis. More mature nephrons were located in the deeper part of the cortex, close to the juxta-medullary junction. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Glomeruli changed their size and shape, while the tubules changed their length and convolution. Renal cortex became wider and contained the more mature glomeruli and the more convoluted tubules. The volume density of the tubular component of the nephron increased continually from 10.53% (LM IVa) to 27.7% (LM X). Renal corpuscles changed their volume density irregularly during gestation, increasing from 13% (LM IVa) to 15.5% (LM IVb). During the increase of gestational age, the volume density of corpuscular component of the nephron decreased to 11.7% (LM VIII), then went on increasing until the end of the intrauterine development (LM X) when corpuscles occupied 16.73% of the cortical volume. The volume density of the developing nephrons (corpuscular and tubular portion) showed the significant positive correlation (r = 0.85; p<0.01) with gestational age. CONCLUSION: The present study was one of few quantitative studies of the human developing nephron. Knowledge about the normal development of the human kidney should be important for the future medical practice.     

Influence of manufacturing procedure on stability of Unguentum contra perniones preparations

BACKGROUND: Application of various technological procedures for the manufacture of officinal preparation ointment against chilblains (Unguentum contra perniones) produce essential variations in the quality and stability of the final product. Changing the sequence of admixing active substances into the ointment base indicated the presence of incompatibility between the active substances, as well as between the active substances and the ointment base components. The aim was to examine the influence of various technological manufacturing procedures on quality and stability of the preparation. METHODS: Changes in the samples of ointments and aqueous solutions of active substances were analysed microscopically. RESULTS: Microscopic analysis of hydrosoluble active substance solutions demonstrated destruction of ichthammol, induced by an acidic medium due to the dissolution of tannin and resorcinol, which is well known from the literature. It also demonstrated the destruction of tannin and resorcinol in aqueous solution, which had not been described in the literature. Application of the prescribed procedure for the manufacturing of ointment against chilblains, conceals the incompatibility reactions due to a slow dissolution of the tannin suspended in the officinal ointment base Unguentum cera lanae. Admixture of an ready-made aqueous solution of tannin caused an instant contact between ichthammol and the acidic medium, which caused the destruction or the complete absence of the formation of emulsion droplets. The problem of incompatibility reactions between lanolin alcohols in the ointment base and ichthammol and resorcinol, as well as the reaction between Peruvian balsam and sulfur from the ichthammol sulfate ion was observed. Numerous incompatibility reactions of ointment against chilblains, components indicated that it was necessary to introduce alterations in both the qualitative and quantitative composition of the preparation. CONCLUSION: Excipient preparation procedure, as well as the technological procedure for incorporation of active ingredients can cause the incompatibilities and therefore the formulation stability problems.     

Keratin 2e: a marker for murine nipple epidermis

Mesenchyme-derived signals influence the unique keratinization and appendage formation programs in specialized skin regions. Interactions between primary mammary mesenchyme and epidermal cells result in the formation of the nipple; however, it is unclear whether this represents a site of regionally specialized epidermis. We profiled the ultrastructure and keratin expression of the murine nipple, and the ventral skin of the K14-parathyroid hormone-related protein (PTHrP) transgenic mouse, which models nipple formation. We found the murine nipple and ventral K14-PTHrP epidermis display expanded suprabasal and granular layers, as well as a thickened cornified layer compared to ventral skin of wild-type littermates. We also observed increased levels of filaggrin in extracts from the ventral epidermis of the K14-PTHrP mouse when compared to that of wild-type littermates. Keratin 2e, previously reported to be expressed in various specialized epidermal sites in the mouse, is expressed in the nipple and the ventral skin of the K14-PTHrP mouse. Keratinocytes grown from the ventral epidermis of the K14-PTHrP mouse or wild-type littermates exhibited identical expression of epidermal markers in vitro, suggesting that the modulated differentiation profile observed in the nipple or the ventral K14-PTHrP skin was dependent on interactions with fibroblasts. The lack of appendages, altered stratification pattern and expression of a specialized keratin suggests that the murine nipple is an example of regionally specialized epidermis.     

Combined early treatment with chelating agents DMSA and CaDTPA in acute oral cadmium exposure

The influence of chelating agents: meso-2,3-dimercaptosuccinic acid (DMSA); calcium trisodium diethylenetriaminepentaacetate (CaDTPA) and their combination on mobilisation of cadmium (Cd) was compared in female albino rats. After oral Cd administration chelators were applied either orally (DMSA) or intraperitoneally (CaDTPA) at various short time intervals after Cd. Three experiments were carried out with four treatment groups in each: 1) Cd (control); 2) Cd+DMSA; 3) Cd+CaDTPA; 4) Cd+DMSA+CaDTPA. Time intervals for chelator treatment after Cd administration were: immediate application in the first, half an hour in the second and one hour in the third experiment. At the end of each experiment cadmium was analysed in kidney and liver. Additionally in experiment 3 essential elements (Fe, Cu, Zn) were also determined in the same organs. In experiment 2 the effect of the treatment on urinary elimination of cadmium, copper and zinc were analysed. Results showed that the efficiency of Cd removal from the body (kidneys and liver) is lower when the time between Cd and chelating agents administration is longer. The two chelators differ in efficiency in mobilizing Cd, with DMSA being more efficient than CaDTPA. The combined therapy with the two chelators gave generally better results. It seems that DMSA which is given orally after oral Cd administration removes this element very efficiently from the gastrointestinal tract. CaDTPA, however, which is given parenterally removes absorbed Cd less efficiently, Organs are not significantly depleted in iron and copper after chelation treatment. Only zinc concentration was, however, significantly lower in the liver and higher in kidneys only after CaDTPA and combined DMSA+CaDTPA chelation.     

Rapid prenatal diagnosis of sickle cell diseases using oligonucleotide ligation assay coupled with laser-induced capillary fluorescence detection

Prenatal diagnosis of sickle cell diseases has been available for several years, and our laboratory has performed over 1000 prenatal diagnoses. However, currently available techniques are labor-intensive and time-consuming, and thus the diagnosis is delayed, making the mother's decision difficult. We describe a rapid, high-throughput technique based on the ligation assay coupled with automated capillary fluorescence detection. This new approach allows the diagnosis of both Hgb S and Hgb C to be available in a few hours. We have utilized this technique in 30 prenatal diagnoses and found it to be in complete agreement with the standard diagnoses.     

Schedule-dependent interaction between vinblastine and cisplatin in Ehrlich ascites tumors in mice

Information on the in vivo antitumor efficiency of the combination of Vinca alkaloids in animal tumor models, especially vinblastine (VLB) with cisplatin [cis-diamminedichloroplatinum(II); CDDP] is very limited. Therefore, the aim of our study was to explore whether antitumor schedule dependence exists for the combination of CDDP and VLB on i.p. Ehrlich ascites tumors in mice. Animals were treated 3 days after tumor transplantation with VLB (0.006 mg/kg) or CDDP (0.05 mg/kg) alone, VLB followed by CDDP, and CDDP followed by VLB. The time interval between i.p. injections of the drugs was 24 h. Cell number was measured by counting viable cells using the trypan blue exclusion assay, cell platinum content by electrothermal atomic absorption spectrometry, DNA distribution pattern using flow cytometry, apoptosis by flow-cytometric terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and cell morphology. Combination of CDDP and VLB resulted in additive interaction when VLB preceded CDDP as determined from cell survival data 24 h after completion of the therapy and in increased platinum content (two times) compared with the same combination in a reverse schedule (CDDP given before VLB), which resulted in antagonism. None of the treatment combinations induced apoptosis. We propose that the observed increase in antitumor effectiveness is mainly due to higher platinum accumulation in tumor cells, which we unambiguously demonstrated by measurement of platinum content in the tumor cells, leading to increased cytotoxicity as well as to cell cycle-dependent effects of VLB and CDDP.