GSK-3 kinase a putative therapeutic target in trypanosomatid parasites

ABSTRACT Trypanosomatids are an important group of parasites that predominate in tropical and subtropical areas of the planet, which cause diseases that are classified as forgotten and neglected by the world health organization. In this group of parasites, we find Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma brucei rhodesiense and Leishmania spp, for which there is no vaccine available, and its control has focused mainly on pharmacological treatment. Due to the poverty situation where these diseases are found and the biological complexity of these parasites, there are multiple variables to control, including the diversity of species, the complexity of their life cycles, drug resistance, cytotoxicity, the limited use in pregnant women, the high costs of treatment and the little-known pharmacological mechanisms of action, among others. It is therefore necessary to find new strategies and approaches for the treatment of these parasitic diseases. Among these new approaches is the rational search for new targets based on the allosteric inhibition of protein kinases, which have been little studied in trypanosomatids. Among these kinases, we find Glycogen Synthase Kinase-3 (GSK-3), a kinase of great pharmacological interest, which is under intense basic and clinical research by pharmaceutical companies for the treatment of cancer. This kinase, highly studied in the PI3K/AKT/mTOR pathway signaling in humans, has an orthologous gene in these parasites (GSK-3 s), which has proven to be essential for them in response to different challenges; Therefore, it is notable to increase research in this kinase in order to achieve a broad structural and functional characterization in the different species of trypanosomatids.

Importancia de la tripanosomiasis africana para Cuba / Importance of African Trypanosomiasis for Cuba

Introducción: La tripanosomiasis africana humana es producida por protozoos del género Trypanosoma y transmitida fundamentalmente por la picadura de la mosca tse-tsé. En el último siglo ha habido varias epidemias en el África, pero dado que el número de nuevos casos notificados había disminuido, la hoja de ruta de la OMS para las enfermedades tropicales desatendidas fijó el objetivo de su eliminación como problema de salud pública para 2020. Muchos de los países donde Cuba presta colaboración internacionalista son endémicos, por lo que los colaboradores están expuestos al riesgo de padecer y enfrentar esta enfermedad. Objetivo: Realizar una actualización clínica y epidemiológica de la entidad para alertar sobre la posibilidad de la aparición en áreas endémicas y la presencia de casos importados en Cuba. Métodos: Se realizó una revisión bibliográfica en la base de datos Medline/PubMed y en artículos relevantes relacionados con el tema, de los últimos años; también hemos tomado como referencia las notas descriptivas de tripanosomiasis africana de la OMS en el 2020, así como textos clásicos de medicina interna y la plataforma búsqueda ClinicalKey. Información, análisis y síntesis: Se hizo una detallada exposición de la enfermedad y la conducta terapéutica; una breve reseña de los casos importados y del país de procedencia, además del peligro que presenta la aparición de casos importados para Cuba. Conclusiones: La enfermedad es una entidad potencialmente mortal, endémica en países donde existe colaboración cubana. Es necesario tener presente el diagnóstico de esta enfermedad para un abordaje terapéutico adecuado(AU)

Introduction: Human African trypanosomiasis is produced by protozoa of the genus Trypanosoma and transmitted mainly by the bite of the tsetse fly. There have been several epidemics in Africa in the last century, but as the number of new reported trypanosomiasis cases has decreased, the WHO roadmap for neglected tropical diseases had targeted their elimination as a public health problem by 2020. Many of the countries where Cuba provides internationalist collaboration are endemic, so the collaborators are exposed to the risk of suffering and facing this disease. Objectives: To carry out a clinical and epidemiological update of the entity and warn about the possibility of the appearance in endemic areas and the presence of imported cases in Cuba. Methods: a bibliographic review was carried out in the Medline / Pub Med database and in relevant articles related to the subject, from recent years; we have taken the 2020 WHO African Trypanosomiasis descriptive notes as a reference, as well as classic internal medicine texts and the ClinicalKey search platform. Information, Analysis and Synthesis: A detailed exposition of the disease and the therapeutic behavior was made; a brief review of imported cases and the country of origin, in addition to the danger posed by the appearance of imported cases for Cuba. Conclusions: This is a potentially fatal entity, endemic in countries where there is Cuban collaboration. It is necessary to bear in mind the diagnosis of this disease for an adequate therapeutic approach(AU)

Evaluation of antitrypanosomal properties and apoptotic effects of ochrolifuanine from Dyera costulata (Miq.) Hook.f against Trypanosoma brucei brucei

@#Trypanosoma brucei parasites are flagellated kinetoplastid protozoan which is responsible for Human African Trypanosomiasis (HAT). Current chemotherapy drugs have a number of side effects and drug resistance has emerged as a major issue in current treatment. Active bisindole alkaloid compound ochrolifuanine was previously isolated from the leaves of Dyera costulata. In vitro antitrypanosomal activity of ochrolifuanine against Trypanosoma brucei brucei strain BS221 showed strong activity with an IC50 value of 0.05 ± 0.01 µg/ml. We compared the effect of ochrolifuanine and reference compound staurosporine in T. b. brucei apoptosis. The apoptosis-inducing activity of ochrolifuanine was evaluated using TUNEL assay and cell cycle analysis. Trypanosoma brucei brucei was shown to undergo apoptotic cells death as demonstrated by the appearance of several conical hallmarks of apoptosis. Ochrolifuanine was found to induce apoptosis in parasites in a dose- and time-dependent manner. The cell cycle study revealed 0.025 and 0.05 µg/ml of ochrolifuanine arrested the growth of T. b. brucei at two different growth phases (G0/G1 and in S phases). While at concentration 0.10 µg/ml arrested at the G2/M phase. In conclusion, the results indicate that ochrolifuanine displayed an antitrypanosomal effect on T. b. brucei by inducing apoptosis cell death and causing the arrest of parasite cells at different growth phases. The results suggested that ochrolifuanine may be a promising lead compound for the development of new chemotherapies for African trypanosomiasis.

Follow - up prognostic study on two imported patients with human African trypanosomiasis / 中国血吸虫病防治杂志

Objective To investigate the prognosis of two rare imported patients with human African trypanosomias (HAT) after treatment in a follow-up study, and to evaluate the therapeutic efficacy, so as to provide insights into the treatment of imported HAT patients. Methods The white blood cells in cerebrospinal fluid samples and the trypomastigotes in cerebrospinal fluid and blood samples were monitored in an imported case with Trypanosoma brucei rhodesiense infection 1, 3, 11 and 25 months post-treatment and in an imported case with T. brucei gambiense infection 1, 3, 8 and 12 months post-treatment to evaluate the therapeutic efficacy and prognosis. Results There were 1, 1, 4 and 2 white blood cells in per μL of cerebrospinal fluid in the case with T. brucei rhodesiense infection 1, 3, 11 and 25 months post-treatment, and there were 3, 6, 4 and 3 white blood cells in per μL of cerebrospinal fluid in the case with T. brucei gambiense infection 1, 3, 8 and 12 months post-treatment. In addition, no trypomastigotes were identified in the cerebrospinal fluid or blood samples of either case with T. brucei rhodesiense or T. brucei gambiense infection. Conclusion Following standardized treatment, two imported cases with human African trypanosomiasis cases recover satisfactorily, without any signs of relapse.

Progress of researches on the interaction between parasitic infections and host cell autophagy / 中国血吸虫病防治杂志

Autophagy, a conserved intracellular degradation system, is a specific life phenomenon in eukaryocytes. Autophagy is widely accepted as a pathway that double-membrane autophagosomes envelop and sequester intracellular cytoplasmic components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients. Autophagy may be triggered by starvation and a diverse range of pathogens, including parasites. Following infection with intracellular parasites, host cells may eliminate parasites by autophagy. However, parasites may develop self-defense mechanisms, and promote the self-growth and -development by host cell autophagy. This review describes the advances in the interplay between parasitic infections and host cell autophagy. Understanding autophagy is of great significance for the management of parasitic infections and the development of antiparasitic drugs.

Evidence for regulated expression of Telomeric Repeat-containing RNAs (TERRA) in parasitic trypanosomatids

The Telomeric Repeat-containing RNAs (TERRA) participate in the homeostasis of telomeres in higher eukaryotes. Here, we investigated the expression of TERRA in Leishmania spp. and Trypanosoma brucei and found evidences for its expression as a specific RNA class. The trypanosomatid TERRA are heterogeneous in size and partially polyadenylated. The levels of TERRA transcripts appear to be modulated through the life cycle in both trypanosomatids investigated, suggesting that TERRA play a stage-specific role in the life cycle of these early-branching eukaryotes.

Blood Profil of Dogs Experimentally Infected with Single Trypanosoma brucei, Ancylostoma caninum and Conjunct Trypanosoma brucei and Ancylostoma caninum and Treatment with Diminazene Aceturate and Mebendazole.

The present study was designed to ascertain the level of haematological alterations in single Trypanosoma brucei (T. brucei), Ancylostoma caninum (A. caninum) and conjunct infections of both parasites in dogs and effect of treatment with diminazene aceturate and mebendazole on haematology. Sixteen dogs grouped into 4 of 4 members each were used in the study. Group 1 (GPI) was uninfected (control), GPII was infected with A. caninum, GPIII was infected with T. brucei and GPIV was infected with conjunct infections of T. brucei / A. caninum. Post acclimatization, GPII and GPIV were infected with A. caninum, 2 weeks after GPIII and GPIV were infected with T. brucei. By week 6 post infection, GPII and GPIV were treated with 100 mg of mebendazole given twice daily for 3 days and a repeat given 2 weeks later. GPIII and GPIV were also treated with diminazene aceturate at 7 mg/kg once. Treatment was repeated at week 8 and 9 of the experiment. There was a significant (p < 0.05) decreases in pack cell volume (PCV), haemoglobin concentration (Hb), red blood cell count (RBC) in all the experimental groups (GPII, GPIII and GPIV). The decreases were more in the conjunct group (GPIV) compared to the others. A significant (p < 0.05) decrease in white blood cell (WBC) count was recorded in all the experimental groups (GPII, GPIII and GPIV). It was reflected in significant (p <0.05) decreases in lymphocytes, neutrophil, monocyte, basophil counts in T. brucei infected group. Conversely there were significant (p <0.05) increases in neutrophil, eosinophil, monocyte and basophil count but a decrease in lymphocyte count in A. caninum group. The haematological alterations were more in T. brucie group compared to the A. caninum group. Similarly the effect was more in the conjunct T. brucei /A. caninum group compared to the single T. brucei. Treatment with 7 mg/kg diminazene aceturate and 100 mg mebendazole given once daily for 3 days caused some improvement in haematology. These findings would enhance clinicians’ knowledge of the effect of single and mixed infections of T. brucei and A. caninum in dogs.

Clinical Effects of Mixed Infection of Trypanosomes and Ancylostoma caninum in Dogs and Treatment with Diminazene and Mebendazole (Nigeria).

The socio-economic importance of trypanosomosis and ancylostomosis in both humans and animal necessitated the investigation of the clinical signs of single and conjunct infection of both parasites in dogs. Sixteen dogs grouped into 4 of 4 members each were used in the study. GROUP I was uninfected dogs (control), GROUP II was infected with Ancylostoma caninum GROUP III was infected with Trypanosoma brucei (T. brucei), GROUP IV was mixed infections of Trypanosoma brucei and Ancylostoma caninum (T. brucei/A. caninum). Post acclimatization, Ancylostoma caninum infection was done on GPII and GPIV. Two weeks later Trypanosoma brucei infections was done on GPIII and superimposed on GPIV. Three weeks post trypanosome infection; GPIII and GPIV were treated with 7 mg/kg diminazene aceturate (Veribin®, CEVA Sante Animale- La Ballasteiére 33501 Libourne Cedex, France) x intramuscularly x once. Mebendazole (Vermin®, Janssen-Cilag Ltd 50 - 100 Holmers Farm Way, High Wycombe, Bucks, HP12 4EG UK) at 100 mg x per os twice daily for 3 days was used only on GPII and GPIV and a repeat treatment given 2 weeks later. Prepatent period of T. brucei infection was 5.00±1.30 days in single infection and 3.00±1.40 days in conjunct infection of T. brucei and A. caninum. Persistent parasitaemia resulted in repeated treatment with diminazene aceturate at 7 mg/kg and mebendazole at 100 mg twice daily for 3 days. The predominant signs revealed include; fluctuation in weight, lethargy, vomition, enlargement of popliteal lymphnodes, pyrexia, oedema of lower jaw and ocular discharges, enlarged abdomen, anaemia, cornea opacity and slight emaciation. The clinical signs were most severe in GPIV compared to GPIII. The egg per gram of faeces (EPG) in GPII was significantly higher than the mixed infection (GPIV). Treatment only slightly improved clinical manifestations. In conclusion, most signs shown were consistent with trypanosomosis in dogs except abdominal enlargement which is a complication of A. caninum. Clinical signs therefore could serve as a diagnostic tool in the treatment of both conditions in dogs.

Renal and Hepatic Dysfunctions in Early Phase of Experimental Trypanosoma brucei Infection of Nigerian Pigs.

Aim: The effects of infection with Trypanosoma brucei on renal and hepatic functions in early phase of disease were studied in experimentally infected pigs. The aim of this study was to identify serum biochemical changes that could serve as biomarkers of early renal and hepatic dysfunctions and also serve as basis for therapeutic management of T. brucei infections in man and animals. Study Design: A total of 15 growing pigs aged between 6 and 12 months old were used for the study. The pigs were selected at random into two groups. Group one was made up of seven animals and served as the infected group. The pigs were each infected with 1 x 106 parasites in 2mls of normal saline subcutaneously. The second group, made up of six animals, served as the un-infected control group. Place and Duration of Study: The pigs were housed in insect proof pens for two months while the experiment lasted. Methodology: Blood for serum obtained through venipuncture of the anterior venacava was used for determination of the serum total proteins, albumin, creatinine and urea concentrations as well as activities of alanine and aspartate aminotransferase post infection. Results: After infection there was a sharp increase in Total proteins (P = .05) accompanied by decrease in albumin but increase in globulin concentrations on Day 5. Increases in, serum creatinine and Blood Urea Nitrogen (BUN) concentrations and, activities of Alanine and Aspartate aminotransferases also occurred from this day. Conclusion: It was concluded that decrease in serum albumin concentration alongside increase in creatinine and urea levels as well as those of alanine and aspartate aminotransferase activities may be biomarkers of early onset of renal and hepatic pathology and determinants of ability to achieve self-cure from anemia in T. brucei infections of man and animals. This underscores the relevance of erythropoietin use in chemotherapy of African trypanosomiasis and the roles of renal and hepatic integrity in trypanotolerace.

Sequence Homology Studies of Phospholipase A2-like Gene from Bloodstream form of Trypanosoma brucei.

Aim: This work focused on the sequence homology studies of the enzyme, phospholipase A2 (PLA2), in Trypanosoma brucei obtained from the blood of bull in Federe, Plateau State, Nigeria, West Africa Place and Duration of Study: Department of Biochemistry, University of Jos, Nigeria; Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria, Department of Biotechnology, NVRI, Vom, Nigeria; between June 2009 and September 2011. Methodology: T. brucei grown in rats were harvested and separated using diethyl amino ethyl (DEAE) cellulose chromatography. From the parasites’ genomic DNA the PLA2-like gene was amplified using consensus primers. The amplicon was cloned unto pMal-2cE vector and confirmed using direct PCR and restriction enzyme analyses. The PLA2 gene and translated protein sequences were studied using National Center for Biotechnology Information (NCBI) Conserved Domain Search Tool and Conserved Domain Architectural Retrieval Tool Results: Analyses of the 1344bp gene sequence using bioinformatics tools showed that it is very closely related to PLA2 sequences of T. brucei (TREU 927) and T. b. gambiense. Motifs that are unique to PLA2 (FSHGL) and lipases (GHSFG) were found to be present in the query sequence. The domains present in the studied sequence agreed closely with those of the human platelet activating factor acetyl hydrolase (PAF-AH). There was also a good sequence resemblance with PLA2s from T. cruzi, Metarhizium amisop, Metarphizium acridu and PAF-AH in terms of architecture. Conclusion: The PLA2-like gene isolated from the blood stream form of Trypanosoma brucei and studied was found to posses the domains and motifs unique to PLA2s and lipases and so homology was established among the proteins.

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

In vitro and In vivo Antitrypanosomal Effects of Petroleum Ether, Chloroform and Methanol Extracts of Artemisia maritima Linn.

Petroleum ether, chloroform and methanol extracts of the whole plant of Artemisia maritima Linn were studied in vitro and in vivo for antitrypanosomal activity against Trypanosoma brucei brucei in Swiss albino mice. The extracts were also screened for phytochemicals/secondary metabolites. All the extracts showed trypanocidal activity against T. brucei brucei in vitro with the petroleum ether extract showing the highest activity. The in vivo study revealed that only the chloroform extract A. maritima exhibited antitrypanosomal activity. This extract at a dose of 100mg/kg body weight significantly (p<0.05) reduced the parasitemia in T. brucei brucei infected mice when compared with the other treatment groups. The chloroform extract of A. maritima at this dose reduced the level of parasitemia to 26%. This reduction in the level of parasitemia is statistically significant (p<0.05) compared to the other treatment groups and the untreated control group. The result of the phytochemical analysis revealed that the extracts contain secondary metabolites like flavonoids, terpenoids, steroids, anthraquinones and alkaloids. The presence of these secondary metabolites in this plant might be responsible for the antitrypanosomal activity exhibited by its extracts.

In vitro and in vivo Antitrypanosomal Effects of Methanol and Aqueous Extracts of Picralima nitida.

The methanol and aqueous extracts of the leaves, fruits, seeds, stem bark and roots of Picralima nitida were studied in vitro and in vivo for activity against Trypanosoma brucei brucei in Swiss albino mice. Phytochemicals studies were also conducted for all the plant extracts. The methanol extracts showed appreciably high in vitro and in vivo antitrypanosomal activities compared to the aqueous extracts of the plant. The methanol extract of the root exhibited the highest in vitro antitrypanosomal activity followed by the methanol extract of seed of Picralima nitida. Motility of Trypanosoma brucei brucei was stopped by the methanol extract of the root after 10 min, while the methanol extract of the seed of Picralima nitida stopped the motility of Trypanosoma brucei brucei at 15 min. The methanol extract of the root of Picralima nitida showed the highest in vivo antitrypanosomal activity at 100 mg/kg body weight. The extract cleared the parasite completely from the T. brucei brucei infected Swiss albino mice after day 3 of treatment. There was a statistically significant difference (p<0.05) when the level of parasitemia of the animals treated with the methanol extract of the root of Picralima nitida were compared with the other treatment groups and the untreated control. The phytochemicals detected in these extracts are tannins, flavonoids, alkaloids, steroids, terpenoids, saponins and cyanide glycosides. The in vitro and in vivo antitrypanosomal activity exhibited by these extracts might be attributed to these phytochemicals.

Effect of diminazene aceturate, levamisole and vitamin C combination therapy in rats experimentally infected with Trypanosoma brucei brucei

OBJECTIVE@#To investigate the effect of diminazene aceturate (DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.@*METHODS@#Thirty adult male albino rats, randomly assigned into 6 groups (A-F) of 5 rats each were used. They were either infected with 1×10(6) trypanosomes intraperitoneally (groups A-E) or uninfected (group F). The different groups were treated respectively as follows: group A-with 3.5 mg/kg DA; group B-3.5 mg/kg DA and 7.5 mg/kg levamisole; group C-3.5 mg/kg DA and 100 mg/kg vitamin C; and group D-3.5 mg/kg DA and 7.5 mg/kg levamisole and 100 mg/kg vitamin C. Group E was left untreated. Parameters assessed include: rectal temperature, body weight changes, packed cell volume (PCV), Haemoglobin concentration (Hb), total leucocyte count (TLC) differential leucocyte count (DLC), parasitaemia, clinical signs and survivability.@*RESULTS@#Average pre-patent period of 5 days was recorded. Parasites in the blood were cleared in all treated groups (A-D) within 48 hours post treatment (PT). Untreated rats in group E died between 25 and 32 days post infection (PI). Relapse was not recorded in all the treated groups (A-D). The initial reduction in PCV, Hb, TLC and increases in rectal temperature following infection were reversed by the treatments. The rats that received drug combinations (groups B, C and D) showed faster and higher recovery rates than the uninfected control and group A.@*CONCLUSIONS@#Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.

Xylopioxyde and other bioactive kaurane-diterpenes from Xylopia aethiopica Dunal (Annonaceae).

A new cytotoxic ent-kaurane-type diterpene named xylopioxyde (16,17-epoxy-15-oxo-ent-kauran-19-oic acid) has been isolated from the fruits of Xylopia aethiopica Dunal (Annonaceae) together with three known compounds, namely 15α-acetoxy-ent-kaur-16-en-19 oic acid (xylopic acid), 15-oxo-ent-kaur-16-en-19-oic acid and ent-kaur-16-en-19-oic acid. Xylopic acid, obtained in a good amount, has been successively converted in moderate to good yields into 15-hydroxy-ent-kaur-16-en-19-oic acid, 15-oxo-ent-kaur-16-en-19-oic acid and two new selective trypanocidal stereoisomers of 15-acetoxy-16,17-ent-epoxy-kauran-19-oic acid, respectively. All the compounds except the synthetic epoxides displayed cytotoxic effects on the mammalian fibroblast cell line MRC-5 as well as inhibitory effects on the growth of the bloodstream forms of Trypanosoma brucei brucei cells (strain 241).

Anti-trypanosomal effect of Peristrophe bicalyculata extract on Trypanosoma brucei brucei-infected rats

Objective: To investigate the in vitro and in vivo effect of whole plant extracts of Peristrophe bicalyculata on Trypanosoma brucei brucei-infected rats. Methods: The experiment was divided into two phases: In the first phase, the anti-trypanosomal activity of the hot water, cold water, methanol and butanol extracts of the whole plant were determined by incubating with Trypanosoma brucei brucei. The cold water extract was partially-purified and the anti-trypanosomal activity of the fractions determined. In the second phase, Trypanosoma brucei brucei-infected rats were treated with fraction 2c for nine days. Packed cell volume (PCV), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triacylglycerol (TAG), aspartate aminotransferase, alanine aminotransferases (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels were determined at the end of the experiment. Results:Cold water extract immobilized 90%of the parasites after 60 min of incubation, and fraction 2c completely immobilized the parasites after 35 min. It significantly increased PCV in Trypanosoma brucei brucei-infected rats. Decreased TC, TAG, HDL and LDL levels of infected rats increased significantly when rats were treated with the fraction, while elevated levels of total bilirubin and ALT also decreased. The difference in urea, direct bilirubin and ALP was not significant when infected rats were compared to rats in other groups. Conclusions:The ability of the plant to ameliorate the infection-induced biochemical changes calls for detailed investigation of the potentials of the plant for antitrypanosomiasis drug delivery.

Effects of Allium sativum Bulb Extract, Diminazene Aceturate and Their Combination on Parasitaemia, and Biochemical Indices in Rats Experimentally Infected with Trypanosoma Brucei Brucei.

Thirty five clinically healthy albino rats of both sexes weighing between 100 – 120grams were used to study the effects of Allium sativum bulb extract in combination with diminazene aceturate on parsitemia and biochemical indices in trypanosome brucei brucei infection. The rats were divided in to seven groups (A-G) of five rats each. All the infected rats developed Parasitemia five days post infection. Weakness, increase respiratory rate, rough hair coat Biochemical changes at interval and possible deaths were the major parameters which were carefully observed. All the treatment commenced at the onset of parasitemia by day five post infection. Sub therapeutic dose of Allium sativum at 20mg/kg/bw in combination with 1.7mg/kg/bw of diminazene aceturate (Group C),diminazene aceturate at single standard dose of 3.5mg/kg/bw (Group B) caused a significant reduction (P<0.05) in parasitemia. The liver function enzymes ALT AST level in rats infected and not treated showed significant increase liver function enzymes (Group A) while those treated with standard and sub therapeutic dose (Group BCD) respectively. Had their liver function enzymes towards normal, compare with control (Group G).Its trypanocidal activity was assessed through daily examination of blood parasite, sub therapeutic doses of Allium sativum bulb extracts and its combination appear to be more effective in reducing severity of trypanosome brucei brucei infection and provide alternative in reducing the toxicity of existing trypanocide.

Trypanosomatid comparative genomics: contributions to the study of parasite biology and different parasitic diseases

In 2005, draft sequences of the genomes of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, also known as the Tri-Tryp genomes, were published. These protozoan parasites are the causative agents of three distinct insect-borne diseases, namely sleeping sickness, Chagas disease and leishmaniasis, all with a worldwide distribution. Despite the large estimated evolutionary distance among them, a conserved core of ~6,200 trypanosomatid genes was found among the Tri-Tryp genomes. Extensive analysis of these genomic sequences has greatly increased our understanding of the biology of these parasites and their host-parasite interactions. In this article, we review the recent advances in the comparative genomics of these three species. This analysis also includes data on additional sequences derived from other trypanosmatid species, as well as recent data on gene expression and functional genomics. In addition to facilitating the identification of key parasite molecules that may provide a better understanding of these complex diseases, genome studies offer a rich source of new information that can be used to define potential new drug targets and vaccine candidates for controlling these parasitic infections.

Observations on estrus as monitored by receptivity to mating activity and pattern of vaginal exfoliates in trypanosoma brucei ­ infected WAD goat does synchronized with Estrumate® / Observaciones sobre el estro monitorizado por la receptividad a la actividad de apareamiento y el patrón de exfoliación vaginal en cabras WAD infectadas por trypanosoma brucei sincronizadas con Estrumate®

The effects of experimental Trypanosoma brucei infection on receptivity to mating activity and pattern of vaginal exfoliates were monitored using twenty-one adult WAD goats which were synchronized with double injection, seven days apart of Estrumate®. The twenty-one goats consisted of 3 bucks and 18 does. The does were randomly divided into control group 'A' having 10 does and test group 'B' with 8 does. The goats were fed with Elephant grass in the morning and commercial feed containing 15.23 percent CP at the rate of 0.25kg/head in the afternoons. Freshwater was provided ad libitum. Results showed that while all the control does were observed to stand to be mounted and mated, none of the infected does did. Also, the pattern of the mean percentage vaginal exfoliated cell types encountered between the control and infected doe groups were converse. While parasabal cells changed from 2.90±0.03 percent during proestrus through 3.05 +/- 0.46 percent during estrus to 2.42 +/-0.08 percent at diestrus in the control does, it changed from 22.07 +/- 0.56 percent during expected proestrus through 8.48 +/- 0.05 percent during expected estrus to 28.05 +/-1.09 percent respectively in the infected does. In like manner, intermediate cell changed from 11.10 +/- 0.03 percent during proestrus through 11.10 +/- 0.31 percent during estrus to 1.21 +/- 1.00 percent during diestrus in control does while it changed from 27.27 +/- 0.08 percent during expected proestrus through 42.37 +/- 2.39 percent during expected estrus to 40.24 +/- 1.06 percent during expected diestrus in infected does. Similarly, superficial cells changed from 56.25 +/- 0.75 percent during proestrus through 63.70 +/- 1.05 percent during estrus to 7.37 +/- 0.01 percent during diestrus while it changed from 0.00 percent during expected proestrus through 3.39 +/- 0.02 percent during expected estrus to 63.70 +/- 1.05 percent during estrus to 6.10 +/- 0.01 percent during expected diestrus. In the control does, the ...

Los efectos de la infección experimental por Trypanosoma brucei sobre la receptividad a la actividad de apareamiento y el patrón de exfoliación vaginal fueron monitoreados utilizando 21 cabras WAD adultas sincronizadas con doble inyección, a los siete días de diferencia de Estrumate®. De las 21 cabras utilizadas eran 3 machos y 18 hembras. Las hembras se dividieron al azar en grupo control "A" con 10 sujetos y un grupo de prueba "B" con 8. Las cabras fueron alimentadas con pasto y alimento comercial que contenía 15,23 por ciento de CP en tasa de 0,25kg/por cabeza en las tardes. Agua fresca fue proporcionada ad libitum. Los resultados mostraron que mientras todos las cabras del grupo control pudieron ser montadas y acopladas, ninguna de las infectadas pudo. Además, fue contradictorio el patrón de la media porcentual de los tipos de células vaginales exfoliadas encontradas entre los grupo control e infectadas. Mientras que las células parabasales cambiaron desde un 2,90 +/- 0,03 por ciento durante el proestro, al 3,05 +/- 0,46 por ciento durante el estro y 2,42 +/- 0,08 por ciento al diestro en el grupo control, el grupo infectado cambió desde un 22,07 +/- 0,56 por ciento durante el proestro, al 8,48 +/- 0,05 por ciento durante el estro y 28,05 +/- 1,09 por ciento al diestro. De la misma forma, las célula intermedias cambiaron de un 11,10 +/- 0,03 por ciento durante el proestro, al 11,10 +/- 0,31 por ciento durante el estro y al 1,21 +/- 1,00 por ciento durante el diestro en el grupo control, mientras que en el grupo infectado pasó del 27,27 +/- 0,08 por ciento durante el proestro, al 42,37 +/- 2,39 por ciento durante el estro y al 40,24 +/- 1,06 por ciento durante el diestro. Las células superficiales pasaron desde un 56,25 +/- 0,75 por ciento durante el proestro, 63,70 +/- 1,05 por ciento durante el estro, hasta un 7,37 +/- 0,01 por ciento durante el diestro, mientras en el grupo infectado pasaron de un 0.00 por ciento durante el proestro, al 3,9 +/- 0,02 p...