An effective trypanocidal agent.
A species of Trypanosome hemoflagellates that is carried by tsetse flies and causes severe anemia in cattle. These parasites are also found in horses, sheep, goats, and camels.
Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA.
Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.
A disease endemic among people and animals in Central Africa. It is caused by various species of trypanosomes, particularly T. gambiense and T. rhodesiense. Its second host is the TSETSE FLY. Involvement of the central nervous system produces "African sleeping sickness." Nagana is a rapidly fatal trypanosomiasis of horses and other animals.
Infection in cattle caused by various species of trypanosomes.
A group of tick-borne diseases of mammals including ZOONOSES in humans. They are caused by protozoa of the genus BABESIA, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick IXODES SCAPULARIS.
A genus of tick-borne protozoan parasites that infests the red blood cells of mammals, including humans. There are many recognized species, and the distribution is world-wide.
Phenanthridines are a class of heterocyclic aromatic organic compounds consisting of two benzene rings fused to a pyridine ring, which have been extensively studied for their biological activities, including antimalarial, antibacterial, and antitumor properties.
Amidines are organic compounds containing the functional group consisting of a nitrogen atom connected to two carbon atoms by double bonds, with the remaining two bonds attached to hydrogen and any other organic substituent.
Substances that are destructive to protozoans.
Proteins involved in the transport of NUCLEOSIDES across cellular membranes.
A genus of flagellate protozoans found in the blood and lymph of vertebrates and invertebrates, both hosts being required to complete the life cycle.
A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina).

The formation of DNA interstrand cross-links by a novel bis-[Pt2Cl4(diminazene aceturate)2]Cl4.4H2O complex inhibits the B to Z transition. (1/80)

We present data demonstrating that the cytotoxic compound [Pt2Cl4(diminazene aceturate)2]Cl4.4H2O (Pt-berenil) circumvents cisplatin resistance in ovarian carcinoma cells. The analysis of the interaction of Pt-berenil with linear and supercoiled DNA indicates that this compound induces the formation of a large number of covalent interstrand cross-links on DNA and that this number is significantly higher than that produced by cis-diamminedichloroplatinum(II) (cis-DDP). Renaturation experiments, interstrand cross-link assays, and electron microscopy indicate that the kinetics of DNA interstrand cross-link formation caused by Pt-berenil binding is faster than that caused by cis-DDP at similar levels of platinum bound to DNA. Furthermore, the number of DNA interstrand cross-links in Pt-berenil-DNA complexes is influenced by supercoiling. Circular dichroism experiments show that Pt-berenil strongly inhibits the B-DNA-to-Z-DNA transition of poly(dG-m5 dC). poly(dG-m5dC) at salt concentrations (3 mM MgCl2) at which the native methylated polynucleotide readily adopts the Z-DNA conformation, which suggests that the induction of interstrand cross-links by Pt-berenil inhibits the Z-DNA transition. On the basis of these results, we propose that bis(platinum) compounds with structure similar to Pt-berenil may act as blockers of DNA conformational changes and may also display activity in cisplatin-resistant cells.  (+info)

Effect of clindamycin therapy on phagocytic and oxidative activity profiles of spleen mononuclear cells in Babesia rodhaini-infected mice. (2/80)

Spleen weight, the number of spleen mononuclear cells, and their phagocytic activity in groups of Babesia rodhaini-infected mice treated with diminazene diaceturate and clindamycin increased significantly in the early stage of treatment, and then decreased in the final stage of treatment to approximately the pre-infection level. The number of F4/80-positive macrophages and their oxidative activity per mean whole-spleen weight also increased significantly during the course of treatment in comparison with the untreated group. The increases in the clindamycin-treated group were more prominent than those in the group treated with diminazene diaceturate, suggesting the effectiveness of clindamycin therapy for murine babesiosis.  (+info)

Heterogeneous DNA binding modes of berenil. (3/80)

Isothermal titration calorimetry (ITC) profiles of berenil bound to different DNAs show that, despite the strong preference of berenil for AT-rich regions in DNA, it can bind to other DNA sequences significantly. The ITC results were used to quantify the binding of berenil, and the thermodynamic profiles were obtained using natural DNAs as well as synthetic polynucleotides. ITC binding isotherms cannot be simply described when a single set of identical binding sites is considered, except for poly[d(A-T)2]. Ultraviolet melting of DNA and differential scanning calorimetry were also used to quantify several aspects of the binding of berenil to salmon testes DNA. We present evidence for secondary binding sites for berenil in DNA, corresponding to G+C rich sites. Berenil binding to poly[d(G-C)2] is also observed. Circular dichroism experiments showed that binding to GC-rich sites involves drug intercalation. Using a molecular modeling approach we demonstrate that intercalation of berenil into CpG steps is sterically feasible.  (+info)

Discriminating small molecule DNA binding modes by single molecule force spectroscopy. (4/80)

Drugs may interact with double stranded DNA via a variety of binding modes, each mode giving rise to a specific pharmacological function. Here we demonstrate the ability of single molecule force spectroscopy to discriminate between different interaction modes by measuring the mechanical properties of DNA and their modulation upon the binding of small molecules. Due to the unique topology of double stranded DNA and due to its base pair stacking pattern, DNA undergoes several well-characterised structural transitions upon stretching. We show that small molecule binding markedly affects these transitions in ways characteristic to the binding mode and that these effects can be detected at the level of an individual molecule. The minor groove binder berenil, the crosslinker cisplatin and the intercalator ethidium bromide are compared.  (+info)

Suppression of antibody response to Leptospira biflexa and Brucella abortus and recovery from immunosuppression after Berenil treatment. (5/80)

Zebu cattle infected with either Trypanosoma congolense EATRO 1800 or Trypanosoma vivax EATRO 1721 had suppressed humoral immune responses to Leptospira biflexa injected intravenously and to attenuated Brucella abortus injected subcutaneously. T. congolense infections were more suppressive than T. vivax infections. In cattle infected with T. vivax, the suppression of immune responses to both bacterial immunogens was abrogated when the animals were treated with Berenil at the time of antigen administration. In cattle infected with T. congolense, simultaneous Berenil treatment at the time of vaccination abolished the suppression of immune response to L. biflexa, and lessened but did not abrogate the suppression of immune response to B. abortus.  (+info)

Determination of affinity, stoichiometry and sequence selectivity of minor groove binder complexes with double-stranded oligodeoxynucleotides by electrospray ionization mass spectrometry. (6/80)

Electrospray mass spectrometry was evaluated regarding the reliability of the determination of the stoichiometries and equilibrium association constants from single spectra. Complexes between minor groove binders (Hoechst 33258, Hoechst 33342, DAPI, netropsin and berenil) and 12mer oligonucleotide duplexes with a central sequence (A/T)4 flanked by G/C base pairs were chosen as model systems. To validate the electrospray ionization mass spectrometry (ESI-MS) method, comparisons were made with circular dichroism and fluorescence spectroscopy measurements. ESI-MS allowed the detection of minor (2 drug + DNA) species for Hoechst 33258, Hoechst 33342, DAPI and berenil with duplex d(GGGG(A/T)4GGGG). d(CCCC(A/T)4CCCC), which were undetectable with the other techniques. Assuming that the duplexes and the complexes have the same electrospray response factors, the equilbrium association constants of the 1:1 and 2:1 complexes were determined by ESI-MS, and the values show a good quantitative agreement with fluorescence determined constants for Hoechst 33258 and Hoechst 33342. It is also shown that ESI-MS can quickly give reliable information on the A/T sequence selectivity of a drug: the signal of a complex is directly related to the affinity of the drug for that particular duplex. The potential of ESI-MS as a qualitative and quantitative affinity screening method is emphasized.  (+info)

Clinical and neuroinflammatory responses to meningoencephalitis in substance P receptor knockout mice. (7/80)

Human African trypanosomiasis, also known as sleeping sickness, affects the CNS at the late stage of the disease. Untreated the disease is invariably fatal, and melarsoprol, the only available and effective treatment for CNS disease, is associated in up to 10% of cases with a severe post-treatment reactive encephalopathy (PTRE), which can itself cause death. We used a reproducible mouse model of the PTRE to investigate the pathogenesis and treatment of this condition. Mice infected with Trypanosoma brucei brucei and treated subcuratively with diminazene aceturate develop a severe meningoencephalitis that closely resembles PTRE. We previously reported that substance P plays an important role in PTRE. We investigated the effect of disrupting the gene encoding for the NK1 receptor in mice on the clinical and neuroinflammatory response in this model. After induction of PTRE, NK1-/- mice showed a significant reduction in clinical impairment compared with NK1+/+ mice, but the severity of the neuroinflammatory response was significantly greater in NK1-/- mice. To explore the mechanisms of this dissociated phenotype, we treated infected NK1-/- mice with antagonists to NK2 and NK3 receptors, either singly or in combination. While none of these antagonist treatments altered the clinical score, combined treatment with the NK2 and NK3 antagonists significantly reduced the neuroinflammatory grading score in the NK1-/- mice. Thus, the clinical and neuroinflammatory responses to parasite invasion can be mediated by different pathways, and, importantly, the neuroinflammatory response is altered by alternative tachykinin receptor usage. These findings could be exploited to develop novel anti-inflammatory therapies in Human African trypanosomiasis by modulating the NK1 receptor as well as the parasite.  (+info)

A rapid, reliable method of evaluating growth and viability of intraerythrocytic protozoan hemoparasites using fluorescence flow cytometry. (8/80)

Fluorescence flow cytometry was employed to assess the potential of a vital dye, hydroethidine, for use in the detection and monitoring of the viability of hemoparasites in infected erythrocytes, using Babesia bovis as a model parasite. The studies demonstrated that hydroethidine is taken up by B. bovis and metabolically converted to the DNA binding fluorochrome, ethidium. Following uptake of the dye, erythrocytes containing viable parasites were readily distinguished and quantitated. Timed studies with the parasiticidal drug, Ganaseg, showed that it is possible to use the fluorochrome assay to monitor the effects of the drug on the rate of replication and viability of B. bovis in culture. The assay provides a rapid method for evaluation of the in vitro effect of drugs on hemoparasites and for analysis of the effect of various components of the immune response, such as lymphokines, monocyte products, antibodies, and effector cells (T, NK, LAK, ADCC) on the growth and viability of intraerythrocytic parasites.  (+info)

Diminazene is an antiparasitic drug, primarily used in veterinary medicine to treat and prevent infections caused by trypanosomes, which are protozoan parasites that can affect both animals and humans. The drug works by inhibiting the protein synthesis of the parasite, leading to its death.

In human medicine, diminazene is used as an alternative treatment for acute African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense in areas where other treatments are not available or have failed. It is usually given by intramuscular injection and is often used in combination with suramin.

It's important to note that the use of diminazene in human medicine is limited due to its potential toxicity, and it should only be administered under the supervision of a healthcare professional.

Trypanosoma congolense is a species of protozoan parasite that belongs to the genus Trypanosoma. It is the primary causative agent of African animal trypanosomiasis (AAT), also known as Nagana, which affects both wild and domestic animals in sub-Saharan Africa.

The life cycle of T. congolense involves two main hosts: the tsetse fly (Glossina spp.) and a mammalian host, such as cattle, sheep, goats, or wild animals. The parasite is transmitted to the mammalian host through the bite of an infected tsetse fly. Once inside the host's body, T. congolense multiplies in various bodily fluids, including blood, lymph, and cerebrospinal fluid, causing a range of symptoms such as fever, anemia, weight loss, and weakness.

In severe cases, AAT can lead to death, particularly in young or debilitated animals. The disease has significant economic impacts on agriculture and livestock production in affected regions, making it a major public health concern.

Trypanocidal agents are a type of medication specifically used for the treatment and prevention of trypanosomiasis, which is a group of diseases caused by various species of protozoan parasites belonging to the genus Trypanosoma. These agents work by killing or inhibiting the growth of the parasites in the human body.

There are two main types of human trypanosomiasis: African trypanosomiasis, also known as sleeping sickness, which is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense; and American trypanosomiasis, also known as Chagas disease, which is caused by Trypanosoma cruzi.

Trypanocidal agents can be divided into two categories:

1. Drugs used to treat African trypanosomiasis: These include pentamidine, suramin, melarsoprol, and eflornithine. Pentamidine and suramin are used for the early stages of the disease, while melarsoprol and eflornithine are used for the later stages.
2. Drugs used to treat American trypanosomiasis: The main drug used for Chagas disease is benznidazole, which is effective in killing the parasites during the acute phase of the infection. Another drug, nifurtimox, can also be used, although it has more side effects than benznidazole.

It's important to note that trypanocidal agents have limited availability and are often associated with significant toxicity, making their use challenging in some settings. Therefore, prevention measures such as avoiding insect vectors and using vector control methods remain crucial in controlling the spread of these diseases.

Pentamidine is an antimicrobial drug that is primarily used to treat and prevent certain types of pneumonia caused by the parasitic organisms Pneumocystis jirovecii (formerly known as P. carinii) and Leishmania donovani. It can also be used for the treatment of some fungal infections caused by Histoplasma capsulatum and Cryptococcus neoformans.

Pentamidine works by interfering with the DNA replication and protein synthesis of these microorganisms, which ultimately leads to their death. It is available as an injection or inhaled powder for medical use. Common side effects of pentamidine include nausea, vomiting, diarrhea, abdominal pain, and changes in blood sugar levels. More serious side effects can include kidney damage, hearing loss, and heart rhythm disturbances.

It is important to note that the use of pentamidine should be under the supervision of a healthcare professional due to its potential for serious side effects and drug interactions.

African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease caused by the protozoan Trypanosoma brucei. It is transmitted to humans through the bite of an infected tsetse fly (Glossina spp.). The disease has two stages: an early hemolymphatic stage characterized by fever, swollen lymph nodes, and skin rashes; and a late neurological stage characterized by sleep disturbances, personality changes, and motor abnormalities. If left untreated, it can be fatal. The disease is endemic in sub-Saharan Africa, where an estimated 65 million people are at risk of infection.

Bovine trypanosomiasis, also known as Nagana, is a parasitic disease that affects cattle and other animals. It is caused by various species of the protozoan parasite Trypanosoma, which are transmitted through the bite of tsetse flies (Glossina spp.).

The disease is characterized by fever, anemia, weight loss, decreased milk production, abortion in pregnant animals, and eventually death if left untreated. The parasites invade the bloodstream and lymphatic system, causing damage to various organs and tissues.

Bovine trypanosomiasis is a major constraint to livestock production in sub-Saharan Africa, where it affects millions of animals and causes significant economic losses to farmers and pastoralists. Control measures include the use of trypanocidal drugs, insecticide-treated cattle, and the reduction or elimination of tsetse fly populations through various methods such as trapping and habitat modification.

Babesiosis is a disease caused by microscopic parasites of the genus Babesia that infect red blood cells. It is typically transmitted to humans through the bite of infected black-legged ticks (Ixodes scapularis). The incubation period for babesiosis can range from one to several weeks, and symptoms may include fever, chills, headache, body aches, fatigue, and nausea or vomiting. In severe cases, babesiosis can cause hemolytic anemia, jaundice, and acute respiratory distress syndrome (ARDS). Babesiosis is most common in the northeastern and midwestern United States, but it has been reported in other parts of the world as well. It is treated with antibiotics and, in severe cases, may require hospitalization and supportive care.

Babesia is a genus of protozoan parasites that infect red blood cells and can cause a disease known as babesiosis in humans and animals. These parasites are transmitted to their hosts through the bite of infected ticks, primarily Ixodes species. Babesia microti is the most common species found in the United States, while Babesia divergens and Babesia venatorum are more commonly found in Europe.

Infection with Babesia can lead to a range of symptoms, from mild to severe, including fever, chills, fatigue, headache, muscle and joint pain, and hemolytic anemia (destruction of red blood cells). Severe cases can result in complications such as acute respiratory distress syndrome, disseminated intravascular coagulation, and renal failure. Babesiosis can be particularly severe or even fatal in individuals with weakened immune systems, the elderly, and those without a spleen.

Diagnosis of babesiosis typically involves microscopic examination of blood smears to identify the presence of Babesia parasites within red blood cells, as well as various serological tests and PCR assays. Treatment usually consists of a combination of antibiotics, such as atovaquone and azithromycin, along with anti-malarial drugs like clindamycin or quinine. In severe cases, exchange transfusions may be required to remove infected red blood cells and reduce parasitemia (the proportion of red blood cells infected by the parasite).

Preventive measures include avoiding tick-infested areas, using insect repellents, wearing protective clothing, and performing regular tick checks after spending time outdoors. Removing ticks promptly and properly can help prevent transmission of Babesia and other tick-borne diseases.

Phenanthridines are a class of heterocyclic aromatic organic compounds that consist of a phenanthrene core (a polycyclic aromatic hydrocarbon made up of three benzene rings) fused with a pyridine ring (a six-membered ring containing five carbon atoms and one nitrogen atom). They have the chemical formula C12H9N.

Phenanthridines are important in medicinal chemistry because some of their derivatives exhibit various biological activities, such as antitumor, antibacterial, antifungal, anti-inflammatory, and antiviral properties. Some well-known phenanthridine derivatives include the chemotherapeutic agents amsacrine and doxorubicin, which are used to treat various types of cancer.

It's worth noting that while phenanthridines have important medical applications, they can also be toxic or harmful if not handled properly. Therefore, it's essential to follow proper safety protocols when working with these compounds in a laboratory setting.

Amidines are organic compounds that contain a functional group with the structure R-C=N-R, where R can be an alkyl or aromatic group. This functional group consists of a carbonyl (C=O) group and a nitrogen atom (N) connected to two organic groups (R).

In medical terminology, amidines are not commonly used. However, some amidine derivatives have been investigated for their potential therapeutic properties. For example, certain amidine compounds have shown antimicrobial, anti-inflammatory, and antiviral activities. Some of these compounds have also been studied as potential drugs for the treatment of various diseases, including cancer, cardiovascular disease, and neurological disorders.

It is important to note that while some amidines may have therapeutic potential, they can also be toxic at high concentrations and should be handled with care.

Antiprotozoal agents are a type of medication used to treat protozoal infections, which are infections caused by microscopic single-celled organisms called protozoa. These agents work by either killing the protozoa or inhibiting their growth and reproduction. They can be administered through various routes, including oral, topical, and intravenous, depending on the type of infection and the severity of the illness.

Examples of antiprotozoal agents include:

* Metronidazole, tinidazole, and nitazoxanide for treating infections caused by Giardia lamblia and Entamoeba histolytica.
* Atovaquone, clindamycin, and pyrimethamine-sulfadoxine for treating malaria caused by Plasmodium falciparum or other Plasmodium species.
* Pentamidine and suramin for treating African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense or T. b. rhodesiense.
* Nitroimidazoles, such as benznidazole and nifurtimox, for treating Chagas disease caused by Trypanosoma cruzi.
* Sodium stibogluconate and paromomycin for treating leishmaniasis caused by Leishmania species.

Antiprotozoal agents can have side effects, ranging from mild to severe, depending on the drug and the individual patient's response. It is essential to follow the prescribing physician's instructions carefully when taking these medications and report any adverse reactions promptly.

Nucleoside transport proteins (NTTs) are membrane-bound proteins responsible for the facilitated diffusion of nucleosides and related deoxynucleosides across the cell membrane. These proteins play a crucial role in the uptake of nucleosides, which serve as precursors for DNA and RNA synthesis, as well as for the salvage of nucleotides in the cell.

There are two main types of NTTs: concentrative (or sodium-dependent) nucleoside transporters (CNTs) and equilibrative (or sodium-independent) nucleoside transporters (ENTs). CNTs mainly facilitate the uptake of nucleosides against a concentration gradient, using the energy derived from the sodium ion gradient. In contrast, ENTs mediate bidirectional transport, allowing for the equalization of intracellular and extracellular nucleoside concentrations.

Nucleoside transport proteins have been identified in various organisms, including humans, and are involved in numerous physiological processes, such as cell proliferation, differentiation, and survival. Dysregulation of NTTs has been implicated in several pathological conditions, including cancer and viral infections, making them potential targets for therapeutic intervention.

Trypanosoma is a genus of flagellated protozoan parasites belonging to the family Trypanosomatidae. These microscopic single-celled organisms are known to cause various tropical diseases in humans and animals, including Chagas disease (caused by Trypanosoma cruzi) and African sleeping sickness (caused by Trypanosoma brucei).

The life cycle of Trypanosoma involves alternating between an insect vector (like a tsetse fly or kissing bug) and a mammalian host. The parasites undergo complex morphological changes as they move through the different hosts and developmental stages, often exhibiting distinct forms in the insect vector compared to the mammalian host.

Trypanosoma species have an undulating membrane and a single flagellum that helps them move through their environment. They can be transmitted through various routes, including insect vectors, contaminated food or water, or congenital transmission from mother to offspring. The diseases caused by these parasites can lead to severe health complications and may even be fatal if left untreated.

Trypanosoma brucei brucei is a species of protozoan flagellate parasite that causes African trypanosomiasis, also known as sleeping sickness in humans and Nagana in animals. This parasite is transmitted through the bite of an infected tsetse fly (Glossina spp.). The life cycle of T. b. brucei involves two main stages: the insect-dwelling procyclic trypomastigote stage and the mammalian-dwelling bloodstream trypomastigote stage.

The distinguishing feature of T. b. brucei is its ability to change its surface coat, which helps it evade the host's immune system. This allows the parasite to establish a long-term infection in the mammalian host. However, T. b. brucei is not infectious to humans; instead, two other subspecies, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, are responsible for human African trypanosomiasis.

In summary, Trypanosoma brucei brucei is a non-human-infective subspecies of the parasite that causes African trypanosomiasis in animals and serves as an essential model organism for understanding the biology and pathogenesis of related human-infective trypanosomes.

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