PCR-RFLP and DNA sequencing techniques were used for Pyrimethamine (PYR) and Cycloguanil (CYC) resistant mutations. The study results showed that 46 of 58 Plasmodium falciparum isolates were genotype resistant to pyrimethamine (79.31%). Thirty-one isolates were taken in vitro microscopic examination and revealed that 26 of 31 isolates were PYR resistance (83.87%) and 6 of 31 isolates of CYC resistance (19.35%). The resistant levels of these isolates were related to the mutations in DHFR genes
Plasmodium falciparum ; Pyrimethamine ; Chloroguanide ; malaria

The chemotherapeutic efficacy of trimethoprim-sulfamethoxazole (Bactrim) in mice experimentally infected with Toxoplasma gondii was evaluated. The average survival days and survival rate of mice infected intraperitoneally with 1 x 10(5) trophozoites and treated with Bactrim were compared with those of untreated group. The hematologic findings of blood samples of experimental mice were observed for comparison of side effects between Bactrim and pyrimethamine (Daraprim), the latter of which has been one of the favorable drugs for the treatment of toxoplasmosis. The results are summarized as follows: Bactrim showed a strong evidence of potent anti-Toxoplasma activity. The survival rate of mice administered with 24 mg of Bactrim per mouse per day for 7 days, was 83.3 percent, and the rate was increased to 100 percent in mice administered with two-fold concentrated dose of the drug. The average numbers of white blood cells (W.B.C.) in the mouse groups treated with Bactrim or Daraprim were more increased than those only infected with T. gondi . The mice treated with Daraprim, however, showed remarkably decreased numbers of W.B.C. as compared with those treated with Bactrim. The average numbers of red blood cells (R.B.C.) and platelets both in the drug-treated and untreated T. gondii-infected mice were decreased as compared with normal mice. The numbers of R.B.C. in Daraprim-treated mice, however, were more decreased than in Bactrim-treated mice. The average levels of hemoglobin both in the drug-treated and untreated T. gondii-infected mice were decreased, compared with normal mice. But there was no difference in the levels of hemoglobin between Bactrim- and Daraprim-treated groups. In conclusion, trimethoprim-sulfamethoxazole (Bactrim) was proven to be effective and safe for the treatment of murine toxoplasmosis. The efficacy was comparable with pyrimethamine (Daraprim), but bone marrow depression was less severe with Bactrim treatment.
parasitology-protozoa ; Toxoplasma gondii ; toxoplasmosis ; chemotherapy ; trimethoprim-sulfamethoxazole ; pyrimethamine ; mouse ; trimethoprim-sulfamethoxazole ; pyrimethamine

In 1998-2002 year period, those studies were developed in LaoCai, LaiChau, QuangTri, Daklak, GiaLai and KonTum. Malarial patients with P. falciparum without complication were administered orally by a total dose of Chloroquine 25mg/kg in 3 day treating course or an unique dose of sulfadoxin-pyrimethamin.The use of medicines was observed and the parasitic density was monitored within 28 days after the treatment. Results showed the failure rate at almost studied locations
Malaria ; Therapeutics ; Pharmaceutical Preparations ; Malaria, Falciparum ; Drug Resistance ; Chloroquine ; Pyrimethamine

The efficacy of chloroquine or sulfadoxine-pyrimethamine given combined with artesunate was assessed in Vietnamese patients with uncomplicated falciparum malaria from 2 Southern provinces, where there was in vitro evidence that the sensitivity of the parasite to conventional antimalarial therapies had returned in the absence of drug pressure, from October to December of 2000. In Dak Lak province, 57 patients (mean age 9.6 years) were randomized to artesunate-chloroquine (group 1) or artesunate-sulfadoxine/pyrimethamine (group 2). In Binh Phuoc province, 66 patients, who have just migrated in period of 1-7 years (mean age 24.2 years) were assessed with the 2 regimens. The results of 28 days in vivo response were over 96% and lower 52% of Dak Lak and Binh Phuoc respectively. PCR evidence of cure closely paralleled the in vivo results. The successful reintroduction of chloroquine and sulfadoxine-pyrimethamine as artemisinin partner drugs depends heavily on epidemiological and parasite factors
malaria ; Malaria, Falciparum ; Therapeutics ; Pharmaceutical Preparations ; artesunate ; Chloroquine ; Pyrimethamine

Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans. In immunocompetent hosts, the infection is usually asymptomatic and benign. Toxoplasmosis is either congenital or acquired. In general prenatal therapy of congenital toxoplasmosis is beneficial in reducing the ncy of infant infection. Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentration achieved in the placenta. Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection. The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides. Toxoplasmic encephalitis is tbe most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal. However, because of toxicity, the therapeutic efficacy of pyrimethamine sulphonamide combinations may be seriously limited in immunodeficient patients. We have experienced a case of toxoplasmosis during the workup of habitual aborter. So we report this case with a brief review of literatures.
Birds ; Chemoprevention ; Clindamycin ; Encephalitis ; Humans ; Immunocompromised Host ; Infant ; Infant, Newborn ; Mammals ; Placenta ; Pyrimethamine ; Spiramycin ; Toxoplasma ; Toxoplasmosis* ; Toxoplasmosis, Congenital

*Asia, Southeastern ; *Chloroguanide ; *Chloroquine ; *Drug Resistance, Microbial ; *Drug Therapy ; *Malaria ; *Plasmodium falciparum ; *Pyrimethamine ; *Quinacrine ; *Quinine ; *Statistics ; *Adolescent ; *Child

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5 μM) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1–5 μM, but host cells were destroyed at 10–20 μM. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.
Antibodies ; Blotting, Western ; Cell Death ; Epidermal Growth Factor* ; Erlotinib Hydrochloride ; Fluorescent Antibody Technique ; Humans* ; Membranes ; Parasites ; Protein-Tyrosine Kinases ; Pyrimethamine ; Receptor, Epidermal Growth Factor* ; Toxoplasma

Vivax malaria, which was once thought to be eradicable since more than 20 years ago, has made a dramatic resurgence since 1993 in the northern parts of Kyeonggi-do in the background of 0.13 of the annual parasite incidence in the population of 956,773 and 2 positives (0.07%) of asymptomatic parasitaemia among the 2,937 residents of mass blood survey in the area in 1969. The majority of the cases were soldiers infected in several counties located within 5 km from the Demilitarized Zone (DMZ) in 1994. Since then, malaria cases have increased and have tended to expand toward eastern and southern areas. Korean malaria is characterized by asymptomatic parasitaemia with long prepatent period, so malaria cases, including those manifesting as general fever should be treated with a combination of chloroquine and pyrimethamine to prevent the completion of sporogonic cycle in the mosquitoes. For the most effective control of vector mosquitoes, residual insecticides should be applied in the military houses and animal shelters with thermal fogging, including the control of the pre-stages of physiological age of the mosquitoes within 25 km from the DMZ. It is strongly suggested that military uniforms be treated with 0.5% permethrin complex (permethrin 39%+cyfluthrin 1%) or permethrin formulation. Further genetic studies are desired to determine the subspecies of Plasmodium vivax because Korean strain of malaria is likely to be a complex form of Plasmodium vivax vivax and Plasmodium vivax hibernans.
Animals ; Chloroquine ; Culicidae ; Fever ; Gyeonggi-do ; Humans ; Incidence ; Insecticides ; Korea* ; Malaria* ; Malaria, Vivax ; Military Personnel ; Parasites ; Permethrin ; Plasmodium vivax ; Pyrimethamine ; Weather

Pyrimethamine(PYR) produces reversible infertility in mice. The antifertility effect of PYR is due to its antifolate action. PYR causes male infertility in Balb C mice in a dose dependent manner. The present study was performed to determine DNA synthesis of germ cell in mice treated with PYR. For 6-8 weeks adult Balb C mice were administered a PYR dose of 100mg- 200mg/ kg/day suspended in vegetable oil.10 control mice received only vegetable oil without PYR. After 7 weeks administration 28.6% of mice(4/14) administered a PYR dosage of 100mg/kg were infertility, whereas all of those(4/4), 200mg/kg/day were infertile. Morphologic changes of the testis induced by orally administered PYR were spermatogenic arrest and depopulation of germ cell. The incorporation of thymidine into DNA of germ cells was studied by using autoradiography after intraperitoneal injection of 15 Ci of methyl-3H-thymidine. Synthesis of DNA takes place in interphase and early prophase of mitotic phase of germ cell. The synthesis of DNA in spermatogonia reduced in all stage of spermatogenesis in mice treated with PYR due to spermatogenic arrest, compared with that of control mice. These results suggest that reduced synthesis of DNA in spermatogonia by PYR administration caused hypospermatogenesis. PYR represents further approach toward development of male contraceptive.
Adult ; Animals ; Autoradiography ; DNA* ; Germ Cells* ; Humans ; Infertility ; Infertility, Male ; Injections, Intraperitoneal ; Interphase ; Male ; Mice* ; Mice, Inbred BALB C ; Oligospermia ; Prophase ; Pyrimethamine* ; Spermatogenesis ; Spermatogonia ; Testis* ; Thymidine ; Vegetables

The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
Amino Acid Substitution/genetics ; Antimalarials/*pharmacology ; Drug Combinations ; *Drug Resistance ; Haplotypes ; Humans ; Iran ; Malaria, Vivax/*parasitology ; *Mutation, Missense ; Plasmodium vivax/*enzymology/genetics/isolation & purification ; Polymorphism, Genetic ; Pyrimethamine/*pharmacology ; Sulfadoxine/*pharmacology ; Tetrahydrofolate Dehydrogenase/*genetics