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Biomedical subjects

D Bunnag

Publications and source records attributed to D Bunnag.

At least 91 records · Page 5Linked to original sources
PubMed1988

Inhibition of tolbutamide metabolism by antimalarial drugs.

The effects of mefloquine (MQ), the combination of MQ with sulfadoxine-pyrimethamine (MSP), sulfadoxine (S), pyrimethamine (P) quinine (Q) and quinidine (Qd) on in vitro hepatic metabolism has been studied using tolbutamide as a substrate. The hydroxylation of tolbutamide was determined in the presence of variable concentrations of each compound. Tolbutamide hydroxylase activity in control microsomes was 0.20 +/- 0.13 nmole/min/mg microsomal protein at a substrate concentration of 150 microM. All compounds studied inhibited tolbutamide metabolism as shown by a decrease in 4-hydroxytolbutamide formation. The order of potency of the inhibitors was MSP greater than S greater than MQ greater than Q greater than Qd greater than P. MQ, MSP, S, Q, and Qd were examined in detail for the type of inhibition. MQ and Qd were non-competitive inhibitors, whereas MSP and S were competitive inhibitors and Q was an uncompetitive inhibitor of tolbutamide 4-hydroxylation. These data provide more information on the inhibitory potential of some antimalarial drugs on microsomal enzymes in human liver. S has been shown to be a potent inhibitor in vitro and this finding possibly explains the longer T 1/2 and MRT of MQ when co-administered with S in healthy volunteers. Further studies in man should be attempted in order to understand the clinical relevance of the inhibitory potential of the antimalarial drugs.

Adult↗
PubMed1988

Opisthorchis viverrini eggs and adult flukes as nidus and composition of gallstones.

Three cases of opisthorchiasis with calculous cholecystitis was presented. The diagnosis of gallstones was made before praziquantel therapy in 2 cases, and 4 years after treatment in one case. The patients underwent cholecystectomy. Numerous O. viverrini eggs and one dead fluke were found in the bile in one case. A single stone was recovered from each gallbladder. All stones contained O. viverrini eggs. Fragments of flukes were also present in two cases. The stones consisted of a mixture of bilirubin pigment and calcium salts.

Adult↗
PubMed1988

Glucose-6-phosphate dehydrogenase deficiency in Thailand: the influence on the clinical presentation of malaria in male adult patients.

One hundred and ninety-two male malaria patients admitted to two different hospitals within 1 year, were studied. There were 74 malaria cases with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and 118 G-6-PD normal malaria cases, randomly selected as a control group. History of dark urine, and the presence of jaundice, haematocrit, total bilirubin and parasite count on day of admission were not significantly different comparing both groups. The number of observed complications did not differ either. Distinctions were detected in abnormal symptoms and in some laboratory parameters in patients with Plasmodium falciparum infection. G-6-PD deficient patients had significantly less gastrointestinal disturbances (P = 0.006), higher serum glutamic oxalacetic transaminase (P = 0.009) and significantly lower blood urea nitrogen (P = 0.007) when compared with the control group. These findings indicate that G-6-PD deficiency when the variants are aggregated, in male adult patients has no significant influence on the clinical presentation of malaria.

Adult↗
PubMed1988

Effect of praziquantel treatment on antibody levels and lymphoproliferative responses in patients with opisthorchiasis.

The purpose of this study was to explore alternative method(s) to monitor the efficacy of anthelmintic treatment of patients with opisthorchiasis. Therefore, in our initial attempt, we studied the changes in antibody levels and lymphoproliferative responses in O. viverrini infected patients before and 2 months after successful praziquantel treatment. The results showed that although a substantial reduction of the antibody levels occurred after such a treatment, it did not occur in all patients. In those showing reduction, the final level were still above 2 standard deviations of the normal mean value. The reduction was more profound for IgG antibody. With regard to the IgA antibody isotype, the reduction was not as marked. In contrast, IgE antibody levels in most patients not only failed to decline, but instead, showed a tendency to be elevated after praziquantel treatment. Unlike the antibody levels, there was no alteration in the lymphoproliferative response to PHA stimulation and therefore this parameter is not useful for our intended objective. It was suggested that studies of a more specific O. viverrini component may be more reliable than the current method of parasitological examination of eggs in the feces of suspected individuals.

Animals↗
PubMed1987

High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand.

Within two months of treatment for falciparum malaria, Plasmodium vivax infections developed in 58 (33%) of 174 patients who had received a quinine or quinidine regimen and in 46 (32%) of 145 patients who had received mefloquine with inpatient follow-up of more than six weeks. The time to vivax relapse was significantly longer after mefloquine treatment (median 47 days, range 30-65) than after quinine or quinidine treatment (21 days, 15-36; p less than 0.0001). All patients remained outside areas of malaria transmission. These findings suggest a very high rate of double infection in Thailand with acute suppression of vivax by falciparum malaria, and warrant evaluation of radical therapy with primaquine in certain patients with acute falciparum malaria.

Acute Disease↗
PubMed1987

Dynamic alteration in splenic function during acute falciparum malaria.

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

Adult↗
PubMed1987

The pharmacokinetics of mefloquine when given alone or in combination with sulphadoxine and pyrimethamine in Thai male and female subjects.

The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were measured by HPLC at intervals for 42 days. There was considerable interindividual variability in the pharmacokinetic parameters; for example in the male subjects receiving MQ alone peak concentrations ranged between 638 and 2494 ng X ml-1 with a mean concentration of 1442 ng X ml-1. Compared to previously published data on MQ concentrations in Caucasian male subjects, the present study indicates that higher concentrations are achieved in Thai subjects. The only significant difference in kinetic parameters between male and female subjects receiving MQ alone was in the mean residence time (MRT) which was greater in females. However, an analysis of pharmacokinetic parameters following administration of the combination preparation showed that the time to peak (tmax) was significantly reduced in females receiving MSP compared to the corresponding females given MQ alone and males given MSP. When data obtained from all subjects (male and female) receiving either MQ alone or MSP were combined, both MRT and half-life were significantly greater in subjects given MSP. There is therefore some evidence that therapeutic concentrations of MQ are maintained for a longer period of time following MSP administration.

Adult↗
PubMed1987

A competitive radioimmunoassay using a monoclonal antibody to detect the factor X activator of Russell's viper venom.

A radioimmunoassay (RIA) has been developed for the detection of Russell's viper venom in body fluids. This is a competitive binding technique using a monoclonal antibody directed against the factor X activator of Russell's viper venom. The sensitivity of the test in urine was 4 ng/ml, in 0.1% bovine serum albumin-phosphate buffered saline it was 20 ng/ml and in serum it was 5 micrograms/ml. This was adequate to detect venom in the serum of four patients bitten by Russell's viper. Urine from an isolated kidney preparation perfused with Russell's viper venom contained coagulant activity and was positive using the competitive RIA. Testing of sera from other envenomated patients and pure venom from seven other species of snake indigenous to Thailand revealed RIA cross reactivity between cobra venom and Russell's viper venom. In practice, the absence of coagulant activity in cobra venom clearly distinguishes between the two. Although further development is required to elucidate the serum factors interfering with this assay, this is a promising technique, which is of potential value in the diagnosis and investigation of the pathophysiology of Russell's viper envenomation.

Animals↗
PubMed1987

Two-site immunoradiometric assay for detection of Plasmodium falciparum antigen in blood using monoclonal and polyclonal antibodies.

Three systems of immunoradiometric assays (IRMAs), a two-site monoclonal antibody sandwich IRMA (MAb-IRMA), two-site polyclonal antibody-monoclonal antibody sandwich IRMA (PAb-MAb-IRMA), and two-site polyclonal antibody sandwich IRMA (PAb-IRMA), were developed to detect low-grade infections with Plasmodium falciparum. The assays showed good correlation with parasitemia when tested against parasites from in vitro cultures (r = 0.996, 0.994, and 0.998 for MAb-, PAb-MAb-, and PAb-IRMA, respectively), with the ability to detect as few as 0.24, 0.67, and 1.82 parasites per 10(7) erythrocytes, respectively. The assays were specific for P. falciparum, since a serially diluted specimen from a patient with vivax malaria with an initial parasitemia of 0.8% and almost all of the undiluted specimens from five other vivax malaria patients were negative. The assays were performed on patients with falciparum malaria before and after treatment with antimalarial drugs. Before treatment, all 24 patients were positive by all three systems of two-site sandwich IRMAs. Two weeks after treatment, 81.8% (18 of 22) of the patients were positive by microscopic examination, but the IRMA positivity rates were 90.9% (20 of 22), 86.4% (19 of 22), and 81.8% (18 of 22) for MAb-, PAb-MAb-, and PAb-IRMA, respectively. Four weeks after treatment, all 19 patients were negative by microscopic examination, but 52.6% (10 of 19) of the patients were still positive with MAb- and PAb-MAb-IRMA and 31.6% (6 of 19) were positive with PAb-IRMA. Comparison between the three systems of IRMA showed that the MAb-IRMA was superior to the other two systems for three reasons. First, it gave a lower count when tested with blood from healthy individuals. Second, it gave a higher count when tested with blood from patients with falciparum malaria. Third, it gave better correlation with parasitemia when blood from falciparum malaria patients was tested. MAb-IRMA is recommended for use for the detection of low-grade P. falciparum infection.

Adult↗
PubMed1987

Human monoclonal anti-Plasmodium falciparum antibodies produced by stable EBV-transformed lymphocytes from patients with falciparum malaria.

Peripheral blood lymphocytes (PBL) from 10 persons living in a malaria endemic area and 18 patients recovered from falciparum malaria were studied, nine of whom were admitted to the Hospital for Tropical Diseases and the remaining nine patients were from Trad District Hospital. PBL were divided into two portions, one of which was transformed directly by EBV in the presence of cyclosporin A to eliminate T cell suppression and the other was pre-incubated before transformation with the extract of ultrasonically disrupted, schizont-enriched P. falciparum parasites from in vitro culture. The products of transformed cells were tested for antibodies against blood stages and sporozoites and cells from positive wells were cloned and propagated. With antigen pre-stimulation, cells from 212 of 317 wells (64.5%) were transformed, and this level of transformation was not significantly different from that in the absence of antigen stimulation in which 193 of 311 wells (62.5%) showed transformation (p greater than 0.05). In contrast, 85 of 212 (40.2%) clones from antigen prestimulated wells secreted antibodies whereas 18 of 193 (9.3%) wells without prior antigen stimulation did (p less than 0.0001). Only 44 of 103 antibody-positive clones were subjected to further analysis, of which 42 had activities against blood stages and two against sporozoites. Based on indirect immunofluorescent reactivities, our anti-blood stage monoclonal antibodies (MABs) were conformed to group I (21 clones), III (11 clones) and V (5 clones) and group VI (5 clones).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Mefloquine, sulfadoxine, and pyrimethamine in the treatment of symptomatic falciparum malaria: a double-blind trial for determining the most effective dose.

A total of 89 adult male Thai patients who had acute, uncomplicated falciparum malaria were treated in a double-blind randomized trial with a single oral dose of two or three tablets, each consisting of 250 mg mefloquine, 500 mg sulfadoxine, and 25 mg pyrimethamine (MSP). The two-tablet regimen produced a cure rate (S response) of 93%, the three-tablet regimen a cure rate of 98%. The mean duration of parasitaemia for the two- and three-tablet groups was 50 and 29 hours, respectively, while the mean duration of fever was 43 and 40 hours, respectively. Differences between the groups were not statistically significant. Tolerance was good at both dose levels. The main side-effects were abdominal discomfort, nausea, vomiting, dizziness, and diarrhoea, but these were mild, transient, and required no specific treatment. The results of haematological and biochemical investigations and of urinalysis revealed no drug-related changes following administration of MSP. The electrocardiograms of some patients revealed sinus bradycardia or sinus arrythmia, but these conditions were transient, symptomless, and clinically not significant.

Administration, Oral↗
PubMed1987

Flunarizine and verapamil inhibit chloroquine-resistant Plasmodium falciparum growth in vitro.

Using pharmacological properties in relation to the biochemistry of P. falciparum, verapamil, flunarizine, and chlorpromazine which are calcium blockers were selected to test for their antimalarial activity against P. falciparum in vitro. Results revealed that the drugs inhibited parasite population growth in the following order of IC50: verapamil 1 X 10(-6) M, chlorpromazine 3.5 X 10(-6) M, and flunarizine 5 X 10(-6) M. These three calcium blockers have antimalarial effects on chloroquine resistant parasite (alone T9/94) but are less potent when compared with the efficacy of quinine or mefloquine in vitro.

Animals↗