Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats.

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only). Blood and thyroid gland samples were collected at the experimental termination. Serum TSH, fT3, fT4, T3, and T4 levels were measured, and SPINA-GT and SPINA-GD parameters were calculated. In silico analysis, employing the Comparative Toxicogenomic Database and ToppGene Suite portal, aimed to reveal molecular mechanisms underlying the observed effects. Results showed greater sensitivity in the female rats, with significant effects observed at lower doses. Subacute exposure increased TSH, fT3, and T3 levels in females, while subchronic exposure in males decreased TSH and fT3 levels and increased fT4. Subacute exposure induced changes even at allegedly safe doses, emphasizing potential health risks. Histological abnormalities were observed in all the treated groups. In silico findings suggested that toxic metal exposure contributes to thyroid disorders via oxidative stress, disruption of micronutrients, interference with hormone synthesis, and gene expression dysregulation. These results indicate that seemingly safe doses in single-substance research can adversely affect thyroid structure and function when administered as a mixture. These findings highlight the complex impact of toxic metal exposure on thyroid health, emphasizing that adhering to accepted safety limits for single-substance research fails to account for adverse effects on thyroid structure and function upon exposures to metal mixtures.

Pioneering gut health improvements in piglets with phytogenic feed additives.

This research investigates the effects of phytogenic feed additives (PFAs) on the growth performance, gut microbial community, and microbial metabolic functions in weaned piglets via a combined 16S rRNA gene amplicon and shotgun metagenomics approach. A controlled trial was conducted using 200 pigs to highlight the significant influence of PFAs on gut microbiota dynamics. Notably, the treatment group revealed an increased gut microbiota diversity, as measured with the Shannon and Simpson indices. The increase in diversity is accompanied by an increase in beneficial bacterial taxa, such as Roseburia, Faecalibacterium, and Prevotella, and a decline in potential pathogens like Clostridium sensu stricto 1 and Campylobacter. Shotgun sequencing at the species level confirmed these findings. This modification in microbial profile was coupled with an altered profile of microbial metabolic pathways, suggesting a reconfiguration of microbial function under PFA influence. Significant shifts in overall microbial community structure by week 8 demonstrate PFA treatment's temporal impact. Histomorphological examination unveiled improved gut structure in PFA-treated piglets. The results of this study indicate that the use of PFAs as dietary supplements can be an effective strategy, augmenting gut microbiota diversity, reshaping microbial function, enhancing gut structure, and optimising intestinal health of weaned piglets providing valuable implications for swine production. KEY POINTS: • PFAs significantly diversify the gut microbiota in weaned piglets, aiding balance. • Changes in gut structure due to PFAs indicate improved resistance to weaning stress. • PFAs show potential to ease weaning stress, offering a substitute for antibiotics in piglet diets.

Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats.

Biocompatibility of materials is one of the most important conditions for their successful application in tissue regeneration and repair. Cell-surface interactions stimulate adhesion and activation of macrophages whose acquaintance can assist in designing novel biomaterials that promote favorable macrophage-biomaterial surface interactions for clinical application. This study is designed to determine the distribution and number of macrophages as a means of biocompatibility evaluation of two newly synthesized materials [silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposite hydrogels] in vivo, with approval of the Ethics Committee of the Faculty of Veterinary Medicine, University of Belgrade. Macrophages and giant cells were analyzed in tissue sections stained by routine H&E and immunohistochemical methods (CD68+). Statistical relevance was determined in the statistical software package SPSS 20 (IBM corp). The results of the study in terms of the number of giant cells localized around the implant showed that their number was highest on the seventh postoperative day (p.o.d.) in the group implanted with Ag/PVA hydrogels, and on the 30th p.o.d. in the group implanted with Ag/PVA/Gr. Interestingly, the number of macrophages measured in the capsular and pericapsular space was highest in the group implanted with the commercial Suprasorb© material. The increased macrophage number, registered around the Ag/PVA/Gr implant on 60th p.o.d. indicates that the addition of graphene can, in a specific way, modulate different biological responses of tissues in the process of wound healing, regeneration, and integration.

Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach.

Thyroid hormones (TH) are one of the key factors for normal prenatal development in mammals. Previously, we showed that subclinical maternal hypothyroidism leads to premature atresia of ovarian follicles in female rat offspring in the pre-pubertal and pubertal periods. The influence of decreased concentration of TH on primordial follicles pool formation during neonatal and early infantile period of rat pups was not investigated previously. Maternal hypothyroidism during pregnancy has irreversible negative influence on primordial follicles pool formation and population of resting oocytes in female rat offspring. The study was done on neonatal and early infantile control (n-10) and hypothyroid (n-10) female rat pups derived from control (n-6) and propylthiouracil (PTU) treated pregnant dams (n-6), respectively. Ovaries of all pups were removed and processed for light and transmission electron microscopy (TEM). Number of nests, oogonia and oocytes per nest, primordial, primary, secondary and preantral follicles were determined. Screening for overall calcium presence in ovarian tissue was done using Alizarin red staining. Morphology and volume density of nucleus, mitochondria and smooth endoplasmic reticulum (sER) in the oocytes in primordial follicles was also assessed. Caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), both markers for apoptosis, and proliferating cell nuclear antigen (PCNA) for proliferation were determined in oocytes and granulosa cells in different type of follicles. In neonatal period, ovaries of hypothyroid pups had a decreased number of oogonia, oocytes and nests, an increased number of primordial follicles and a decreased number of primary and secondary follicles, while in early infantile period, increased number of primary, secondary and preantral follicles were found. Alizarin red staining was intense in hypothyroid neonatal rats that also had the highest content of dilated sER. Number of mitochondria with altered morphology in both groups of hypothyroid pups was increased. Apoptosis markers have not shown significant difference between groups but PCNA had an increased expression in the oocytes and granulosa cells in primordial follicles of hypothyroid rats. Light and electron microscopy analysis indicate that previously detected premature ovarian follicular atresia in pre-pubertal and pubertal hypothyroid rats is preceded with premature formation of primordial follicles followed by slight changes on sER and mitochondria in examined oocytes, and increased expression of PCNA.

Expression and functional activity of neurotransmitter system components in sea urchins' early development.

Reverse-transcription polymerase chain reaction (RT-PCR) investigation of the expression of the components supposedly taking part in serotonin regulation of the early development of Paracentrotus lividus has shown the presence of transcripts of five receptors, one of which has conservative amino acid residues characteristic of monoaminergic receptors. At the early stages of embryogenesis the expressions of serotonin transporter (SERT) and noradrenaline transporter (NET) were also recognized. The activities of the enzymes of serotonin synthesis and serotonin transporter were shown using immunohistochemistry and incubation with para-chlorophenylalanine (PСРА) and 5-hydroxytryptophan (HTP). Pharmacological experiments have shown a preferential cytostatic activity of ligands characterized as mammalian 5-hydroxytryptamine (5-HT)1-antagonists. On the basis of the sum of the data from molecular biology and embryo physiological experiments, it is suggested that metabotropic serotonin receptors and membrane transporters take part in the regulatory processes of early sea urchin embryogenesis.

Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-ß1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

Severe road traffic injuries and youth: a 4-year analysis for the city of Belgrade.

The objective of this study is to describe severe road traffic injuries (RTIs) in the population under 18 years in Belgrade, the capital of Serbia. We analysed both severe non-fatal and fatal RTIs in children and adolescents under 18 years old in the Belgrade area, during the period 2008-2011. Data sources were the official statistics of the Public Health Institute in Belgrade and forensic-medical records from two paediatric university hospitals and five university hospitals for adults. Using descriptive statistical methods, demographic characteristics, mechanism, type and time of injuries, surgical treatment procedures, injury severity scores (ISS), length of stay and outcome were evaluated. The admission and mortality rates were calculated. Among the total of 379 injured, 256 (67.5%) were male; the average age was 13.0 ± 4.7 (range: 0-18 years). The annual hospital admission rate of RTIs for both sexes decreased in average by 12.6% (95% CI = 9.3%-15.9%). The mean percentage of annual changes of mortality rates was 2.0 %; 95% CI = 1.3%-5.3% (5.7 per 100,000 in 2008, 5.6 in 2009, 4.7 in 2010 and 5.9 in 2011). The highest admission rates and mortality rates were for pedestrians, followed by passengers and cyclists. Accidents occurred most commonly on Monday (18.7%). Among children hospitalised for traffic injuries, 57.8% had head and neck trauma, 30.6% extremity fractures, 5% abdominal injuries, 4.2% chest and 2.4% multiple injuries. The average ISS was 22.4 (SD = 20.4), ranging from 1 to 75. Alcohol in blood was confirmed in 7.4% males and 3.3% females (p > 0.05). The average time of hospital stay was 8.8 days (SD = 16.7), ranging from 1 to 14. The increased rates require implementation of a well-defined national strategy in our country.

Operative treatment of metacarpal and phalangeal fractures with Kirschner wire fixation--a review.

Although hand fractures are most common fractures treated in orthopedic practice, many practicians treat them as trivial injuries. Improperly managed they can cause consequences and impair hand function. Metacarpal and phalangeal fractures are classified based on geometry, anatomic localization and wound presence and treatment depend on mechanism of injury. Many of them can be treated nonoperatively with reposition and immobilization, but in some cases osteosynthesis is a method of choice. Surgeon can choose various range of fixation material, and choice depends on fracture type and surgeons affinity. Kirschner wire fixation is one of the most frequently used operative procedure for hand fracture treatment. It provides good stability, early mobilization and excellent functional result.

Absence of post-lesion reactive gliosis in elasmobranchs and turtles and its bearing on the evolution of astroglia.

In the mature mammalian and avian central nervous systems, neuronal destructions are followed by reactive gliosis, but data on other vertebrates are rather controversial. Mammals and birds belong to different amniote groups (Synapsida and Diapsida, respectively), but exhibit common general features in their glial architecture, mainly the predominance of astrocytes. Two vertebrate groups seem to be in special positions of glial evolution: turtles (Testudiniformes) and skates and rays (Batoidea). The purely ependymoglial system of turtles seems to be the simplest one among the extant amniotes. In skates and rays, true astrocytes are preponderant glial elements, in contrast to the other "anamniotes" (and even to reptiles). We investigated stab wounds by the immunohistochemical detection of GFAP in turtles (Trachemys-formerly Pseudemys-scripta elegans), a skate (Raja clavata) and rays (Dasyatis akajei and Torpedo marmorata). Sharks (Scyliorhinus canicula) as ependymoglia-predominated chondrichthyans, and-for positive controls-rats were also studied. In the elasmobranchs, other astroglial markers: glutamine synthetase and S100 protein were also applied. Neither turtles nor elasmobranchs presented considerable astroglial reactions. Critically surveying the former reports on different vertebrates, these results complete the picture that typical post-lesion reactive gliosis is confined to mammals and birds. Analysis of the astroglial systems from phylogenetic perspective suggests that the capability of forming glial demarcation and scar formation evolved independently in mammals and birds. Predominance of astrocytes is a necessary condition but not sufficient for reactive gliosis. The intense glial reactivity of mammals and birds may be attributed to their complex cerebralization.

Impact of the injury pattern on the pedestrian fatalities in the city of Belgrade.

INTRODUCTION: In the city of Belgrade pedestrians are under the high risk to sustain injuries in the road traffic accidents, they are often with multiple injuries, with long-term treatment and significant consequences. Most of them are in the )senior or in the school age group. METHODS: We present the results of the epidemiological analysis of the mechanism of injury and treatment outcome of the pedestrians who sustained the lower limb injuries and additional, the injuries of the other organic systems. We also analysed the relevant data about the moment of the collision. RESULTS: Regarding the gender, male were significant more injured., in the senior age of life. Patients with multiple injuries, especially with the pelvic injuries or injuries of more than two systems were significant more likely to have a fatal outcome. CONCLUSION: The pedestrians are the most vulnerable group in road traffic accidents. Thus, we need to make actions on two levels: appropriate environment conditions and effective prehospital and hospital treatment.

War-related infected tibial nonunion with bone and soft-tissue loss treated with bone transport using the Ilizarov method.

PATIENTS AND METHODS: This single centre retrospective study reviews the outcomes of 30 war-injured patients with established infected tibial nonunion after sustaining grade IIIB open fractures. Patients were treated by radical bony and soft-tissue resection and bone transport using the Ilizarov bifocal technique, without the use of systemic antibiotics or bone grafting. RESULTS: The series comprised 29 males and 1 female with a mean age of 30.4 years and a mean nonunion of 8.6 months at index operation. Patients had previously undergone a mean of 1.3 operations (range 1-3), and the mean size of tibial defect was 6.9 cm (range 4-11 cm) post radical debridement. Bony union was achieved at the tibial docking sites after a mean of 4.5 months in 29 patients (97%) and frames were worn for a mean of 9.7 months (range 7.2-15 months), giving a mean fixation index of 1.48 months/cm. One patient failed to unite at their tibial docking site. Soft-tissue transport successfully closed the soft-tissue defects in all but four patients, who required split-skin grafting. According to the Paley scoring system 19 patients had excellent bony results, 10 good and 1 poor; the functional results were excellent in 13 patients, good in 14, fair in 2 and poor in 1; and there were 1.4 complications per patient. Over a mean follow-up of 99 months no patient refractured their reconstruction, developed any symptoms or signs of recurrent infection, or required amputation. CONCLUSION: The Ilizarov technique with bone transport continues to be the most versatile, adaptive and effective method of treatment in these complex cases, and can very successfully deal with the associated large soft-tissue and bony defects without the use of routine bone-grafting, systemic antibiotics or soft-tissue flaps.

The management of humeral shaft fractures with associated radial nerve palsy: a review of 117 cases.

PATIENTS AND METHODS: This single center retrospective study reviews the management and outcomes of 117 consecutive patients with humeral shaft fractures and associated radial nerve palsy (RNP) treated over a 20-year period (1986-2006). A total of 101 fractures were managed conservatively and 16 fractures underwent external fixation for poor bony alignment. Sixteen grade 1 and 2 open fractures underwent wound toileting alone. No patients underwent initial radial nerve exploration or opening of the fracture sites. RESULTS: All patients achieved clinical and radiological bony union at a mean of 8 weeks (range 7-12 weeks). There were no complications or pin tract infections in the operated patients. A total of 111 cases had initial spontaneous RNP recovery at a mean of 6 weeks (range 3-24 weeks) with full RNP recovery at a mean of 17 weeks (range 3-70 weeks) post-injury. Fourteen patients had no clinical/EMG signs of nerve activity at 12 weeks and 6 subsequently failed to regain any radial nerve recovery; 2 had late explorations and the lacerated nerves underwent sural nerve cable neurorraphy; and 4 patients underwent delayed tendon transposition 2-3 years after initial injury, with good/excellent functional outcomes. CONCLUSIONS: Humeral fractures with associated RNP may be treated expectantly. With low rates of humeral nonunion, 95% spontaneous nerve recovery in closed fractures and 94% in grade 1 and 2 open fractures, one has the opportunity of waiting. If at 10-12 weeks there are no clinical/EMG signs of recovery, then nerve exploration/secondary reconstruction is indicated. Late tendon transfers may also give good/excellent functional results.

[Epidemiological analysis of demographic characteristics and type of injuries in patients with multiple trauma with respect to conclusive treatment outcome].

INTRODUCTION: Multiple trauma is one of the leading causes of mortality and morbidity in the population of people under 45 years of age. The consequences of multiple trauma have huge epidemiological, social and economic significance. OBJECTIVE: The aim of the paper was to analyse the conclusive treatment outcome of multiply traumatized patients with respect to their sex, age, injury mechanism and type. METHOD: This retrospective study included 100 patients with multiple injuries (ISS > 16) treated in the Emergency Room of the Clinical Centre of Serbia in the course of 2004. Clinical, X-ray, laboratory and numerical presentation methods--scores (ISS and GCS) were used to show the injury severity. RESULTS: Most of the injured were males (80%), and the average age was 40 +/- 20 (5-83). Out of the total number of patients who died, 23 (82%) were males, and 5 (18%) were females. The average age of the patients with fatal outcomes was 48 +/- 21 (8-86). Traffic accidents were the leading cause of injury (59%). The median GCS was 10 +/- 3 (3-15). The average ISS was 30 (20-66) in the surviving patients, and 53 (27-77) in those who died. CONCLUSION: With respect to sex, in most cases multiple trauma affects males (p < 0.01), with the average age of about 40. With respect to injury mechanism, the main cause of the occurrence of multiple trauma is traffic accidents (p < 0.01). There is a statistically significant difference in the values of GCS and ISS relative to the definitive outcome (p < 0.01). Statistical data processing indicated that there was a statistically significant correlation between mortality and type of injury in a given organic system (p < 0.01), but that there was no statistically significant correlation between mortality and age.

Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids.

Amyloid precursor protein (APP) is overexpressed in the developing brain and portions of its extracellular domain, especially amino acid residues 96-110, play an important role in neurite outgrowth and neural cell differentiation. In the current study, we evaluated the developmental abnormalities caused by administration of exogenous APP(96-110) in sea urchin embryos and larvae, which, like the developing mammalian brain, utilize acetylcholine and other neurotransmitters as morphogens; effects were compared to those of beta-amyloid 1-42 (Abeta42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer's Disease. Although both peptides elicited dysmorphogenesis, Abeta42 was far more potent; in addition, whereas Abeta42 produced abnormalities at developmental stages ranging from early cleavage divisions to the late pluteus, APP(96-110) effects were restricted to the intermediate, mid-blastula stage. For both agents, anomalies were prevented or reduced by addition of lipid-permeable analogs of acetylcholine, serotonin or cannabinoids; physostigmine, a carbamate-derived cholinesterase inhibitor, was also effective. In contrast, agents that act on NMDA receptors (memantine) or alpha-adrenergic receptors (nicergoline), and that are therapeutic in Alzheimer's Disease, were themselves embryotoxic, as was tacrine, a cholinesterase inhibitor from a different chemical class than physostigmine. Protection was also provided by agents acting downstream from receptor-mediated events: increasing cyclic AMP with caffeine or isobutylmethylxanthine, or administering the antioxidant, a-tocopherol, were all partially effective. Our findings reinforce a role for APP in development and point to specific interactions with neurotransmitter systems that act as morphogens in developing sea urchins as well as in the mammalian brain.

Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity.

Accumulation of beta-amyloid protein is an Alzheimer's disease hallmark but also may be mechanistically involved in neurodegeneration. One of its cleavage peptides, Abeta42, has been used to evaluate the mechanisms underlying amyloid-induced cytotoxicity and targeting of acetylcholine systems. We studied Sphaerechinus granularis sea urchin embryos which utilize acetylcholine and other neurotransmitters as morphogens. At a threshold concentration of 0.1 microM Abeta42, there was damage to the larval skeleton, accumulation of ectodermal cells in the blastocoele and underdevelopment of larval arms. Raising the Abeta42 concentration to 0.2-0.4 microM produced anomalies depending on the stage at which Abeta42 was introduced: at the first cleavage divisions, abnormalities appeared within 1-2 cell cycles; at the mid-blastula stage, the peak period of sensitivity to Abeta42, gastrulation was blocked; at later stages, there was progressive damage to the larval skeleton, digestive tract and larval spicules, as well as regression of larval arms. Each of these anomalies could be offset by the addition of lipid-permeable analogs of acetylcholine (arachidonoyl dimethylaminoethanol), serotonin (arachidonoyl serotonin) and cannabinoids (arachidonoyl vanillylamine), with the greatest activity exhibited by the acetylcholine analog. These results indicate that sea urchin embryos provide a model suitable to characterize the mechanisms underlying the cytotoxicity of Abeta42, as well as providing a system that enables the rapid screening of potential therapeutic interventions. The protection provided by neurotransmitter analogs, especially that for acetylcholine, points to unsuspected advantages of existing therapies that enhance cholinergic function, as well as indicating novel approaches that may prove protective in Alzheimer's disease.

[Gerhard Küntscher and intramedullary fixation].

Gerhard Küntscher, a German surgeon, was born in Zwickau in 1900. He graduated from the School of Medicine in Jena in 1926. He is renowned for the development of intramedullary fixation as a solution for fixation of fractures in the long bones. He worked in the Freiburg and Hamburg hospitals, but gained most experience during the Second World War, when he was on the Eastern front. In the period 1943-1944, he was the chief surgeon in the German military hospital in Kemio (Finland). After the war, he worked in hospitals is Schleswig and Hamburg until his retirement in 1965. He introduced the method of percutaneous intramedullary nailing in the femur fractures, as well as the interlocking nail, nail fixation of the pertrochanteric fractures and nails for intramedullary osteotomy. He published over 200 papers and 4 books. In his papers, he was often ahead of his time, and today is considered one of the founders of the concept of intramedullary fixation in fractures.

The sea urchin embryo, an invertebrate model for mammalian developmental neurotoxicity, reveals multiple neurotransmitter mechanisms for effects of chlorpyrifos: therapeutic interventions and a comparison with the monoamine depleter, reserpine.

Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mechanisms involved in developmental toxicity and to evaluate different therapeutic interventions corresponding to each neurotransmitter system. Whereas reserpine interfered with all stages of embryonic development, the effects of chlorpyrifos did not emerge until the mid-blastula stage. After that point, the effects of the two agents were similar. Treatment with membrane permeable analogs of the monoamine neurotransmitters, serotonin and dopamine, prevented the adverse effects of either chlorpyrifos or reserpine, despite the fact that chlorpyrifos works simultaneously through actions on acetylcholine, monoamines and other neurotransmitter pathways. This suggests that different neurotransmitters, converging on the same downstream signaling events, could work together or in parallel to offset the developmental disruption caused by exposure to disparate agents. We tested this hypothesis by evaluating membrane permeable analogs of acetylcholine and cannabinoids, both of which proved effective against chlorpyrifos- or reserpine-induced teratogenesis. Invertebrate test systems can provide both a screening procedure for mammalian neuroteratogenesis and may uncover novel mechanisms underlying developmental vulnerability as well as possible therapeutic approaches to prevent teratogenesis.

How against HIV - using immunology or genetic engineering.

How against HIV - using Immunology or Genetic Engineering represents a thinking about the way how to overarch the HIV virus. Namely, by the combination of Immunological and the methods of Genetic Engineering, we could create a new nonreproducible virus which would be a competitor to real HIV for CD4 receptors. Competitors, by their affinity, would be acting in order to engage the CD4 receptors, making them nonaccessible for real HIV. But, at the same time, competitors, by their size, would be just physically covering a small deal of CD4 receptors. That way these free CD4 receptors would also be nonaccessible for real HIV, but accessible for immunomolecules, like, for an example MHC II is. That way the physiological role of CD4 receptors in immunological reactions, would be saved, and that fact would help us in our intention to expel the provirus integrated in its host CD4 lymphocite, by already known immunological mechanisms. Out of the host cell (CD4 Lymphocite) the HIV virus is very responsive for our Immune System and it would be destroyed.