Taliglucerase alfa in Gaucher disease: Description of a Brazilian experience.

We evaluated retrospectively, efficacy and safety of taliglucerase alfa for Gaucher disease in a Brazilian population. Thirteen patients were included for efficacy analysis only one of them naïve to enzyme replacement therapy. All the parameters evaluated remained stable throughout treatment (mean duration 3,5years). Only three patients (out of 35) had to discontinue treatment due to a serious adverse event. In conclusion, treatment with taliglucerase alfa was found to be safe and efficient.

A model for preservation of thymocyte-depleted thymus.

DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

Blind Source Separation in Persistent Atrial Fibrillation Electrocardiograms Using Block-Term Tensor Decomposition With Löwner Constraints.

The estimation of the atrial activity (AA) signal from electrocardiogram (ECG) recordings is an important step in the noninvasive analysis of atrial fibrillation (AF), the most common sustained arrhythmia encountered in clinical practice. This problem admits a blind source separation (BSS) formulation that has been recently posed as a tensor factorization, using the Hankel-based block term decomposition (BTD), which is particularly well-suited to the estimation of exponential models like AA during AF. However, persistent forms of AF are characterized by short R-R intervals and very disorganized (or weak) AA, making it difficult to model AA directly and perform its successful extraction through Hankel-BTD. To overcome this drawback, the present work proposes a tensor approach to estimate QRS complexes and subtract them from the ECG, resulting in a signal that, ideally, only contains the AA component. Such an approach tackles the problem of blind separation of rational functions, which models QRS complexes explicitly. The data tensor admitting a BTD is built from Löwner matrices generated from each lead of the observed ECG. To this end, this paper formulates a variant of the recently proposed constrained alternating group lasso (CAGL) algorithm that imposes Löwner structure on the decomposition blocks. This is done by performing an orthogonal projection, which we explicitly derive, at each iteration of CAGL. Results from experiments with synthetic data show the consistency of the proposed Löwner-constrained AGL (LCAGL) in extracting the desired sources. Experimental results obtained on a population of 20 patients suffering from persistent AF show that the proposed variant outperforms other tensor-based methods in terms of atrial signal estimation quality from ECG records as short as a single heartbeat.

Modified dry bean pod waste (Phaseolus vulgaris) as a biosorbent for fluorescein removal from aqueous media: Batch and fixed bed studies.

This study presents the use of dry bean pods as a solid phase for fluorescein removal from water. The non-pretreated solid phase did not display any sorption properties for the chosen dye. However, interesting sorption properties were observed following a chemical derivative treatment with nitric acid. The study was carried out using both batch and column approaches. Regarding the batch study, all parameters that influence sorption capacity, such, as pH, adsorbent mass, ionic strength, temperature and contact time, were evaluated. A sorptive capacity of 36.80 mg g-1 was obtained in the optimized condition. In the fixed column bed study, the influence of particle size, flow rate and initial concentration of the dye were evaluated through breakthrough curves and a sorptive capacity of 4.35 mg g-1 was obtained. Thermodynamic studies revealed that the adsorption is exothermic and spontaneous. Four different models, Langmuir, Freundlich, Temkin and Redlich-Patterson, were employed. The Akaike information criterion (AIC) was employed to rank the best equilibrium model, which was determined as the Freundlich isotherm. The method was applied to a real sample and the same removal rate was obtained, thus indicating its suitability to wastewater treatment.

Evolution of spray and aerosol from respiratory releases: theoretical estimates for insight on viral transmission.

By modelling the evaporation and settling of droplets emitted during respiratory releases and using previous measurements of droplet size distributions and SARS-CoV-2 viral load, estimates of the evolution of the liquid mass and the number of viral copies suspended were performed as a function of time from the release. The settling times of a droplet cloud and its suspended viral dose are significantly affected by the droplet composition. The aerosol (defined as droplets smaller than 5 µm) resulting from 30 s of continued speech has O(1 h) settling time and a viable viral dose an order-of-magnitude higher than in a short cough. The time-of-flight to reach 2 m is only a few seconds resulting in a viral dose above the minimum required for infection, implying that physical distancing in the absence of ventilation is not sufficient to provide safety for long exposure times. The suspended aerosol emitted by continuous speaking for 1 h in a poorly ventilated room gives 0.1-11% infection risk for initial viral loads of 10 8 - 10 10 copies ml l - l , respectively, decreasing to 0.03-3% for 10 air changes per hour by ventilation. The present results provide quantitative estimates useful for the development of physical distancing and ventilation controls.

Effect of berberine associated with photodynamic therapy in cell lines.

Cervical cancer is a serious worldwide health problem. In view of the potentially harmful effects of current conventional therapies, photodynamic therapy may be an option as it is a minimally invasive therapy and can promote selective cytotoxic activity for neoplastic cells in the target tissue., Berberine (BBR) as an isolated molecule is a natural compound that has antineoplastic properties and potential action as a photosensitizer agent. The purpose of this study was to evaluate the use of berberine as a photosensitizer in photodynamic therapy (PDT) protocols and observe the effects produced by this association in cervical carcinoma cells and in immortalized keratinocytes. Incubation with 2.5 µM berberine promoted less than 10 % of cellular death in both cell lines studied. In addition, by fluorescence microscopy, we demonstrated that berberine was internalized by the cells, and after a period of 48 h, it was still present in the intracellular environment preferentially localized in the cytoplasm. After photodynamic therapy using berberine as a photosensitizer and visible light activation at 447 (±10) nm, we observed a phototoxic effect, which resulted in 19.84 % cell viability for Caski cells and 47.22 % cell viability for HaCaT. Treatment with berberine associated with photodynamic therapy promoted an increase in the production of reactive species of oxygen (ROS) and caspase-3 activity, indicating a preferential cell death mechanism by caspase-dependent apoptosis. Therefore, we demonstrated that berberine is an efficient photosensitizer and that its association with photodynamic therapy may be a potential anticancer treatment strategy for cervical cancer.

A model for preservation of thymocyte-depleted thymus

DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

Antinociceptive effect from Ipomoea cairica extract.

Ipomoea cairica L. Sweet (Convolvulaceae) is used in Brazilian folk medicine for the treatment of rheumatism and inflammations. Ipomoea cairica ethanolic extract (100, 300, 1000 and 3000 mg/kg; per os) induced dose-dependent reduction of response in the formalin test inflammatory phase in mice. The same dose range did not modify neurogenic pain in formalin test, tail-flick reflex latency, carrageenan-induced paw edema, and Rota-Rod test motor performance. From the bio-active fraction 3,5-di-O-caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid were obtained. These compounds have been previously reported to have analgesic and antioxidative effects. A possible explanation for the antinociception is that somehow the compounds present in the extract reduced the release of pro-nociceptive mediators unrelated to carrageenan-induced edema, such as histamine. Interestingly, caffeoylquinic acid derivatives have been reported to inhibit histamine release on in vitro models. The isolated caffeoylquinic acids could explain, at least in part, the antinociceptive effect of Ipomoea cairica polar extract.

Substituição do milho pelo sorgo sobre o desempenho zootécnico e na digestibilidade em coelhos / Replacement of corn by sorghum on zootechnical performance and digestibility in rabbits

O milho é a principal fonte de energia nas dietas animais. Em algumas regiões brasileiras, sua disponibilidade, principalmente na entressafra, é insuficiente para atender à demanda, fazendo com que seu preço se eleve. Neste estudo, objetivou-se avaliar a substituição do milho pelo sorgo sobre o desempenho zootécnico e a digestibilidade em coelhos. Foram utilizados 60 animais machos da raça Nova Zelândia Branco, divididos em três tratamentos: ração base milho (TM); ração base sorgo (TS) e ração base 50% de milho + 50% de sorgo (TMS). No ensaio de desempenho, avaliou-se ganho de peso (GP), consumo de ração (CR), conversão alimentar (CA), coeficientes de digestibilidade da matéria seca (CDMS), proteína bruta (CDPB), fibra em detergente neutro (CDFDN) e fibra em detergente ácido (CDFDA). Observou-se que o CRM, a CA e o GPM não foram afetados pela substituição do milho pelo sorgo, nos níveis de 50% e 100%. Os resultados de digestibilidade demonstraram maiores CDPB e CDFDN na ração base milho, não havendo diferenças entre os demais parâmetros estudados. O sorgo com baixo teor de tanino pode ser usado nas rações de crescimento de coelhos em níveis de substituição de 50% ou 100% da participação do milho, sem prejuízos para o desempenho zootécnico e a digestibilidade.(AU)

Corn is the main source of energy in animal diets. In some Brazilian regions, its availability, especially in the off-season, may be insufficient to meet demand, which causes prices to increase. In this context, the aim of this study was to evaluate the substitution of maize by sorghum on the performance and digestibility of rabbits. Sixty New Zealand White bucks were used, divided in three treatments, maize base ration (TM); based on grain sorghum ration (TS) and base ration 50% corn + 50% sorghum grain (TMS). In the performance test, weight gain (GP), feed intake (CR) and feed conversion ratio (CA) were evaluated. In the digestibility assay, 21 animals were used. The total dry matter (CDMS), crude protein (CDPB), gross energy (EB), neutral detergent fiber (CDFDN) and acid detergent fiber (CDFDA) coefficients were evaluated. There was no significant difference for any of the performance parameters studied (P > 0.05). The digestibility results showed higher CDPB and CDFDN in the corn diet (P <0.05), with no differences between the other parameters studied. Low tannin sorghum can be used in rabbit growth diets at substitution levels of 50% or 100% of maize participation without impairing zootechnical performance and digestibility.(AU)

Simple bit-string model for lineage branching.

We introduce a population dynamics model, where individual genomes are represented by bit strings. Selection is described by death probabilities which depend on these genomes, and new individuals continuously replace the ones that die, keeping the population constant. An offspring has the same genome as its (randomly chosen) parent, except for a small amount of (also random) mutations. Chance may thus generate a newborn with a genome that is better than that of its parent, and the newborn will have a smaller death probability. When this happens, this individual is a would-be founder of a new lineage. A new lineage is considered created if the number of its live descendants grows above a certain previously defined threshold. The time evolution of populations evolving under these rules is followed by computer simulations and the probability densities of lineage duration and size, among others, are computed. These densities show a scale-free behavior, in accordance with some conjectures in paleoevolution, and suggesting a simple mechanism as explanation for the ubiquity of these power laws.

Study of zinc and growth hormone in sickle cell disease.

About 25% of children with sickle cell disease (SCD) have statural deficit and retarded skeletal maturation and pubertal development. These disorders have been attributed to low serum concentrations of zinc. We report the study of serum zinc in 34 patients with SCD, of whom 17 had statural deficit (SCS group) and 17 without growth deficiency (SCN group). They were compared with 20 normal children (N group). GH secretion and thyroid function were investigated in the group with short stature (SCS) in order to rule out GH deficiency and hypothyroidism. The mean serum zinc concentration was 108.45+/-22.888 microg/100 ml in the N group, 87.529+/-30.069 microg/100 ml in the SCN group and 82.765+/-34.766 microg/100 ml in the SCS group. There was a statistically significant difference between the mean of the N group and the mean of the SCN group (p<0.05) but no difference was found between the two groups of patients (N>SCN=SCS). Although there is a well-established zinc deficiency in patients with SCD, the statural retardation found in the SCS group could not be attributed only to zinc deficiency. Many other severe metabolic disturbances are also involved.

A prospective and randomized study using ribavirin as monotherapy for the treatment of naïve patients with chronic hepatitis C.

In order to evaluate the response to ribavirin in previously untreated patients with chronic hepatitic C, 39 patients were selected for a double-blind prospective and randomized trial, and divided into two groups: ribavirin-group (19 patients) and placebo-group (20 patients). Ribavirin was administered orally for 24 weeks (600 mg/day, followed by 1,000 mg/day and 1,200 mg/day each one for 8 weeks). After 3 months of drug administration, the patients were evaluated by measuring biochemical, virologic and histologic responses. After this phase, ribavirin was offered to the patients who had received placebo (second phase). The results showed that the patients who received ribavirin showed a higher reduction in serum alanine aminotransferase (ALT) activity than patients in the placebo group. Among the patients in the ribavirin-group, a complete biochemical response (ALT levels normalized) was observed in 3 patients (16%), and a partial response (reduction greater than 50% of the initial value of ALT activity) in 4 (21%). In the 20 patients in the placebo group, only 1 showed a partial response (5%). In the second phase of the study, among 16 patients who received ribavirin, 4 (25%) showed a complete and 5 (31%) a partial biochemical response. HCV-RNA did not become negative in any patient during the two phases. A reduction in the score of portal and lobular activity was observed in patients who received ribavirin, but statistical analysis did not identify differences. This study showed that ribavirin alone induces a biochemical response (ALT reduction) in some patients with chronic hepatitis C, which may be associated with a reduction in hepatic inflammatory activity reduction, but the changes are not sufficient to recommend initial monotherapy with ribavirin.

[The optimization of the use of economic resources for vaccination against hepatitis B in professionals in the health area]. / Otimização do emprego de recursos econômicos para vacinação contra hepatite B em profissionais da área de saúde.

In order to optimize the employment of financial resources to be allocated for hepatitis B vaccination programs involving health care workers, two different aspects were studied: the need of a pre-vaccination screening and the efficacy of low-doses schedules of HBV vaccine by the intradermal (ID) route. The economical analysis (a cost-minimization study) showed that when the prevalence of immune individuals is higher than 11% it is more cost-effective to perform pre-vaccination screening. This situation was observed in the employees group. For students and doctors vaccination without screening was the best approach. Regarding the schedules, 3 doses of HBV vaccine by the intramuscular (IM) route (group A) were compared to first dose by the ID route and second and third doses by the IM route (group B) and to first and second doses by the ID route and the last dose by the IM route (group C). After the third dose, soroconversion rates in groups A and B (92% and 93%, respectively) and geometric mean titers of antiHBs (1278 UI/L and 789.6 UI/L) were similar, and both were different from group A (p < 0.05), showing that alternative vaccination schedules may be cost-effective.

Clinical disorders observed in anteaters (Myrmecophagidae, Edentata) in captivity.

The major health problems found in 103 captive lesser anteaters (Tamandua tetradactyla) and giant anteaters (Myrmecophaga tridactyla), family Myrmecophagidae, are presented and correlated with management. The most common of 200 recorded clinical disorders involved the digestive system (26%), nutritional deficiency (20%), injury (15.5%), respiratory system (10%), skin (7%) and circulatory system (4.5%), but 13% of the cases were inconclusive. Parasites were identified in 48.5% of faecal samples, mainly the eggs of nematodes (40%), of which the commonest were Trichuris spp (28%) and Strongyloides spp (11%); protozoa (16%), of which the commonest were Eimeria spp (10%), Entamoeba spp (5%) and Giardia spp (1%); and cestodes (8%) and acanthocephalids (1%). Bacteria cultured from the various materials included Salmonella enteritidis, S. cholerasuis, Escherichia coli, Enterobacter aerogenes, Streptococcus spp and Staphylococcus spp. The ectoparasites found were Amblyomma spp and Otodectis spp (Arthropoda, Acaridae).

Clinical problems of sloths (Bradypus sp. and Choloepus sp.) in captivity.

A 20-yr retrospective study of disease prevalence was carried out for 51 sloths (34 Bradypus sp. and 17 Choloepus sp.) at the São Paulo Zoo. A total of 81 clinical disorders were detected, including nutritional (45.7%), digestive (12.3%), and respiratory (12.3%) problems and injuries (6.1%). A definitive diagnosis was not possible in 8.6% of the cases. The incidence of disease varied according to seasonal climate (winter, 32.5%; spring, 24%; summer, 22.9%; autumn, 20.5%), time in captivity (96.4% of diseases occurred within the first 6 mo and 3.6% occurred thereafter), and type of enclosure (quarantine cage, 96.4%; exhibition enclosure, 3.6%). Both young animals (86.7%) and adults (3.2%) were affected. Parasites were identified by fecal examination in 45.4% of animals with clinical illness (Ascaris sp., 80%; Coccidia sp., 20%). Bacteria such as Salmonella enteritidis, Escherichia coli, and Citrobacter freundii were isolated from feces and/or organs. The first 6 mo in captivity are critical for these animals. Proper management and early identification of medical conditions in captivity have implications for sloth population in the wild.

Fatores de risco associados à infecção viral (BoHV-1 e BVDV) em rebanhos leiteiros mestiços com problemas reprodutivos, no município de Uberlândia, MG / Risk factors associated with viral infections (BoHV-1 and BVDV) in crossbreed dairy herds with reproductive failures, Uberlândia, MG

Com frequência, infecções virais são associadas a problemas da reprodução em rebanhos de bovinos de corte e leite de todo o mundo. Este estudo teve como objetivo avaliar variáveis de manejo que possam constituir fatores de risco da infecção por BoHV-1 e/ou por BVDV em rebanhos leiteiros com histórico de problemas da reprodução em vacas mestiças em manejo extensivo e sem histórico de vacinação prévia para o controle de IBR e BVD. Anticorpos neutralizantes anti-BoHV-1, anti-BVDV e para ambos os vírus simultaneamente foram identificados em 62,5% (165/264), 45,1% (119/264) e 31,4% (83/264), respectivamente, das amostras analisadas. Os fatores de risco associados à infecção por BoHV-1 foram rebanhos com número total de fêmeas superior a 100, presença de ordenha mecânica, não utilização de inseminação artificial na reprodução e a compra infrequente de animais. Para BVDV, os fatores de risco foram aptidão mista (leite/corte) do rebanho, presença de ordenha mecânica, ausência de quarentena para os animais recém-adquiridos, presença de piquete de parição e a não utilização de inseminação artificial. Para a infecção simultânea (BoHV-1/BVDV), a presença de ordenha mecânica aumentou o risco em 3,36 vezes, e o uso de inseminação artificial reduziu em 56% o risco de infecção nos rebanhos avaliados.(AU)

Viral infections are frequently associated with reproductive problems in dairy and beef cattle worldwide. The aim of this study was to verify managerial practices that may constitute risk factors associated with infection by BoHV-1 and/or BVDV in dairy herds with a history of reproductive disease in extensively reared dairy cows without a previous history of vaccination against IBR and BVD. Neutralizing antibodies anti-BoHV-1, anti-BVDV or both were detected in 62.5% (165/264), 45.1% (119/264), and 31.4% (83/264), respectively, in the samples analyzed. The risk factors associated with infection by BoHV-1 were herds with more than 100 cows, the presence of mechanical milking, the non-utilization of artificial insemination, and the infrequent acquisition of animals. Risk factors associated with BVDV were dual-purpose herds (milk and beef), these include the utilization of mechanical milking, absence of quarantine for newly acquired animals, the presence of picket calving, and the absence of artificial insemination. For simultaneous infections by both viruses (BoHV-1 and BVDV) the use of mechanical milking increased the chance of infection 3.36-fold while the use of artificial insemination reduced the risk of infection by 56% in these herds.(AU)

Estratégias para minimizar os efeitos de um ambiente térmico adverso para frangos de corte / Strategies to minimize the adverse thermal environment in broiler chickens

O calor limita a produção de frangos de corte. Este trabalho avaliou as interações entre o termocondicionamento precoce (TCP) e o uso do equilíbrio eletrolítico (EE) sobre o desempenho e as características da carcaça das aves. Assim, o balanço eletrolítico (BE = Na + K - Cl) foi ajustado em 350mEq/kg, e a relação eletrolítica (K+Cl)/Na em 3:1, pelo programa PPFR. O experimento foi realizado no setor de Zootecnia da Faculdade de Medicina Veterinária de Araçatuba/Unesp. Alojaram-se 240 pintos machos de um dia de idade, linhagem Cobb-500(r), em bateria metálica com 24 divisões e aquecimento elétrico automático. O delineamento experimental foi inteiramente ao acaso, em arranjo fatorial 2x2, totalizando quatro tratamentos com seis repetições e 10 aves por parcela experimental. O TCP ocorreu no quinto dia de idade, por 24 horas, a 36,5°C, em metade do lote. Posteriormente, as aves foram transferidas para um galpão climatizado e alojadas em boxes, da mesma forma que a outra parcela que não passou pelo TCP. Avaliaram-se os efeitos do estresse calórico crônico (seis horas a 32°C) aplicado do 35º ao 39º dia de idade. Foram monitoradas a temperatura e a umidade do ar, bem como a temperatura de globo negro. Alimentação e água foram fornecidas ad libitum. Calcularam-se os dados de desempenho zootécnico e a taxa de mortalidade das aves. Submeteram-se os resultados à análise de variância e à comparação de médias pelo teste de Tukey. Não houve interação entre o TCP e o EE sobre o desempenho e as características da carcaça das aves. As estratégias, TCP e EE, mostraram-se ineficazes para amenizar os efeitos do estresse calórico crônico em frangos de corte.

Heat limits the production of broilers. This study evaluated the interactions between early thermal conditioning (ETC) and the electrolyte balance (EB) on performance and characteristics of birds' carcass. Thus, the electrolyte balance (BE = Na+ + K+ - Cl-), was set to 350mEq/kg and electrolyte ratio (K+ + Cl-)/ Na+ in 3:1 by the PPFR program. The experiment was carried out at the Animal Science department of the Faculty of Veterinary Medicine of Araçatuba / UNESP. 240 1 day old Cobb-500(r) male chicks were used, lodged in metal batteries with 24 divisions and automatic electric heating. The experimental design was completely randomized in a 2x2 factorial arrangement, totaling 4 treatments with 6 replicates and 10 birds per experimental plot. ETC occurred on the 5th day of age for 24 hours at 36.5°C in half of the batch. Subsequently, these birds were transferred to an environmentally controlled shed and were grown in boxes, in the same way as the other half that had not received ETC treatment. The effects of chronic heat stress (6 hours at 32°C) applied from the 35th through the 39th day of age were evaluated. Temperature and air humidity, as well black-globe temperature were monitored electronically. Food and water were provided ad libitum. The growth performance data and the mortality rate of birds were measured. The results were subjected to analysis of variance and comparison of means was done by Tukey test. There were no interaction effects between ETC and EB on performance and characteristics of birds' carcass. The ETC and EB strategies proved to be ineffective to mitigate the effects of chronic heat stress in broilers.

Modelling survival and allele complementation in the evolution of genomes with polymorphic loci.

We have simulated the evolution of sexually reproducing populations composed of individuals represented by diploid genomes. A series of eight bits formed an allele occupying one of 128 loci of one haploid genome (chromosome). The environment required a specific activity of each locus, this being the sum of the activities of both alleles located at the corresponding loci on two chromosomes. This activity is represented by the number of bits set to zero. In a constant environment the best fitted individuals were homozygous with alleles' activities corresponding to half of the environment requirement for a locus (in diploid genome two alleles at corresponding loci produced a proper activity). Changing the environment under a relatively low recombination rate promotes generation of more polymorphic alleles. In the heterozygous loci, alleles of different activities complement each other fulfilling the environment requirements. Nevertheless, the genetic pool of populations evolves in the direction of a very restricted number of complementing haplotypes and a fast changing environment kills the population. If simulations start with all loci heterozygous, they stay heterozygous for a long time.