This randomized, open-label, balanced, five-treatment, five-period, five-sequence, single-dose and crossover pharmacokinetic study assessed the effect of different types of food on the bioavailability of cefaclor in 18 healthy male volunteers. A single dose of cefaclor, 250-mg capsule was administered at five occasions: after overnight fasting, after two vegetarian (high-fat and low-fat) diets and two non-vegetarian (high-fat and low-fat) diets. Serial blood samples were collected upto 8 h post dose. Serum cefaclor concentrations were determined by a validated HPLC method. AUC values were not significantly affected by food intake, but the T(max) was prolonged and C(max) was decreased, depending on the type of meal. The non-vegetarian diets affected the rate of absorption of cefaclor more than the vegetarian diets. The least decrease in C(max) was produced by low-fat vegetarian diet, while the maximum decrease was produced by high-fat non-vegetarian diet. The results of this study indicate that while the rate of absorption of cefaclor is significantly decreased, the extent of absorption and the rate of elimination are not significantly decreased in the presence of food. As compared to high-fat non-vegetarian diet, the time above MIC50 concentration was significantly increased by low-fat vegetarian diet. The implications of these findings for the large vegetarian Indian population are considerable.

Analysis of Variance↗

PubMedDate not supplied

Comparative effect of different types of food on the bioavailability of cefaclor extended release tablet.

This randomized, six-treatment, six-period, six sequence, single dose, crossover pharmacokinetic study assessed the effect of different types of food on the bioavailability of 500-mg cefaclor extended release tablet in 23 healthy male volunteers. A single dose of cefaclor extended release 500-mg tablet was administered at six occasions: after overnight fasting, after two vegetarian (high-fat and low-fat), two non-vegetarian (high-fat and low-fat) and rice diets. Serial blood samples were collected up to 12 h after dose. Serum cefaclor concentrations were determined by a validated HPLC method. An almost equivalent increase in both Cmax and AUC was observed with both high-fat non-vegetarian and low-fat vegetarian breakfasts. However, when MIC90 values, a pharmacodynamic end-point were compared, the low-fat vegetarian diet fared better than the high-fat non-vegetarian diet. The results obtained favor low-fat vegetarian diet (breakfast) to be taken with cefaclor extended release tablet to achieve maximum benefit in terms of clinical efficacy.

Adult↗

PubMedDate not supplied

Distribution of transferrin (Tf) subtypes in several Mongoloid populations of East Asia.

The distribution of serum transferrin subtypes was determined by PAG electrophoresis and isoelectric focussing in a group of 2288 individuals from 10 Mongoloid populations of East Asia. The sample comprised 857 Chinese from different localities: Singapore (239), Malaysia (228), Taiwan (265), Hong Kong (65), Fouzhou (60); Koreans (332), Filipinos (281), Thais (455), Malays (335) and Indonesians (28). The frequencies of TfC1 varied from 0.73 to 0.79 in the Chinese and from 0.76 to 0.83 in the other Mongoloid populations. TfC3 was observed at a frequency of 0.02 in the Koreans and Chinese from Fouzhou. TfDChi was present in a low frequency (0.01 to 0.03) in all the populations. A low frequency of TfB was also present in all the populations. The phenotypic distribution of transferrin subtypes was at Hardy-Weinberg equilibrium in all the populations.

Adult↗

PubMedDate not supplied

Distribution of group-specific component (Gc) subtypes in several Mongoloid populations of East Asia.

The distribution of group-specific component (Gc) subtypes was determined by isoelectric focussing in thin layer polyacrylamide gels of pH range 4 to 6.5, in a group of 2412 individuals from 10 Mongoloid populations of East Asia. The sample comprised 959 Chinese from different localities (Singapore, 249; Malaysia, 347; Taiwan, 246; Hong Kong, 57; Fuzhou mainland, 60), 338 Koreans, 277 Filipinos, 484 Thais, 330 Malays and 24 Indonesians. The Filipinos and Malays had lower frequencies of Gc2 (0.15 and 0.18) compared to other Mongoloid populations (0.23 to 0.32) and the Chinese (0.24 to 0.32). The frequencies of Gc1F varied from 0.39 to 0.49 in the Chinese and 0.35 to 0.52 in other Mongoloid populations. Low frequency of rarer variants was observed in most of the populations. The average frequency of Gc2 was higher in the Japanese (0.26 +/- 0.01) than in the Chinese (0.24 +/- 0.02), and in Mongoloids of East Asia (0.23 +/- 0.01) and South-East Asia (0.17 +/- 0.01). The average frequencies of Gc1F and Gc1S were similar in the Chinese and Japanese, whereas the Mongoloids of South-East Asia had a much higher frequency of Gc1F and a lower frequency of Gc1S than the Chinese, Japanese and East Asian Mongoloid populations.

Alleles↗

PubMedDate not supplied

Alpha 1-protease inhibitor (PI) subtypes in seven populations of east Asia.

The distribution of serum alpha 1-protease inhibitor (PI) or alpha 1-antitrypsin (alpha 1AT) subtypes was determined by thin-layer isoelectric focusing in a group of 1233 individuals from six Mongoloid populations of East Asia and Dravidian Indians. The sample comprised 385 Chinese from Singapore and 151 Chinese from the Fujien province; 126 Malays; 243 Filipinos; 112 Thais; 56 Koreans and 160 Dravidian Indians. The frequency of PiM1 ranged from 0.65 in the Thais to 0.81 in the Fujien Chinese. The highest frequency of PiM2 was found in the Dravidian Indians (0.28) followed by the Thais (0.25). The frequency of PiM3 was found to vary from 0.03 to 0.07 in these populations. A low frequency of PiF (0.01 to 0.02) and PiS (0.01 to 0.04) was also observed in the Mongoloid populations but absent in the Indians. The PiZ allele was completely absent in all these populations. The phenotypic distribution of PI subtypes was at Hardy-Weinburg equilibrium in all the populations.

Alleles↗

PubMedDate not supplied

Red cell glucose-6-phosphate dehydrogenase phenotypes in several Mongoloid populations of eastern India: existence of a non-deficient fast variant in two Australasian tribes.

A total of 954 subjects of both sexes from nine Mongoloid tribes of eastern India were investigated for the distribution of red cell glucose-6-phosphate dehydrogenase (G6PD) phenotypes by starch-gel electrophoresis. The incidence of Gd- was found to be 8% in the Khasi, 6% in the Nishi, 5% in Apatani and 3% in Adi. The small group of Bodo and the mixed group of other Arunachal tribes had Gd- frequencies of 19% and 15%, respectively. Only one isolated incidence of Gd- was encountered in the Naga, while the Hmar lacked Gd-. The Khasi had a polymorphic frequency (about 4%) of a non-deficient fast variant (GdV) (105% mobility in TEB buffer of pH 8.6). Two heterozygotes of this allele with a combination of common GdB+ were detected in two females. Interestingly, the same allele was reported earlier in another Australasian tribe--the Korkus of central India.

Alleles↗

PubMedDate not supplied

Population genetics of coagulation factor XIIIB in three ethnic groups of Singapore.

The distribution of plasma coagulation factor XXIIB polymorphism was determined by PAG isoelectric focusing and immunoblotting in a group of 670 subjects comprising 375 Chinese, 110 Malays and 185 Indians. The frequencies of FXIIIB*1, FXIIIB*2, and FXIIIB*3 were found to be 0.27, 0.03 and 0.70 in the Chinese; 0.33, 0.05 and 0.64 in the Malays and 0.58, 0.08 and 0.33 in the Indians. The phenotypic distribution of FXIIIB alleles was at Hardy-Weinberg equilibrium in all three populations. A two-dimensional principal-components analysis on the basis of three common alleles at the FXIIIB locus among 19 populations, so far studied, clearly differentiates the Negroid, Mongoloid and Caucasoid populations into three major groups with the exception of Amerindians (Minnesota) and US Blacks showing some Caucasoid influence.

China↗

PubMedDate not supplied

Distribution of plasma alpha-1-B-glycoprotein (A1BG) polymorphism in several populations of the Indian subcontinent.

The distribution of plasma alpha 1B-glycoprotein (A1BG) was determined by a two-dimensional electrophoresis (agarose-polyacrylamide gel) followed by protein staining in a group of 1099 individuals from 11 populations of the Indian subcontinent. The sample comprised 454 from several tribes of Arunachal Pradesh; 76 Bengali Hundus and 88 Bengali Muslims; 179 Tamil Hindus from Singapore and 107 from India; 81 Tamil Muslims, 48 Sinhalese from Sri Lanka and 66 North Indians. Three common A1BG phenotypes (1-1, 1-2 and 2-2) were observed in this study. One each of a new allele (A1BG*7) in heterozygous form (1-7) was detected respectively among Tamil Hindus of India and Singapore. The phenotypic distribution of A1BG alleles was at Hardy-Weinberg equilibrium in all the populations. The frequency of A1BG*2 was in general lower in the Mongoloid tribes of Arunachal Pradesh (0.043-0.104) and North Indians (0.068) compared to that in other Indian populations (0.130-0.171) and Sinhalese (0.208).

Alleles↗

PubMedDate not supplied

New DNA polymorphisms define ethnically distinct haplotypes in the human transferrin receptor gene.

In a study of transferrin receptor (TFR) polymorphism in different ethnic groups using PCR and restriction cleavage we found a new Hin6I polymorphism in intron 7 and confirmed a tentative BanI polymorphism in exon 4 reported by Evans and Kemp [Gene 1997;199:123-131]. In all ethnic groups there was a complete and highly significant (p < 10(-10)) linkage disequilibrium where all BanI 1 alleles were linked to Hin6I 1 alleles. Furthermore in the European populations, but not in the Chinese, there was a close correlation between the three BanI-Hin6I haplotypes and the alleles of a previously described three-allelic RsaI polymorphism in the TFR gene studied by Southern blotting. There were distinct ethnic differences in TFR allele and haplotype frequencies. Thus the Saamis were significantly different from the other European ethnic groups, and the Lithuanians had a significantly increased frequency of the BanI 2-Hin6I 1 haplotype, suggesting that this marker may be informative in tracing prehistoric migrations and admixture by Baltic peoples. The new TFR polymorphisms and haplotypes may also be useful markers in studies of interactions with the transferrin and hemochromatosis genes, the genetic influence on body iron stores and disease associations.

Alleles↗

PubMedDate not supplied

Molecular characterisation of red cell glucose-6-phosphate dehydrogenase deficiency in north-west Pakistan.

233 Pushtoons (129 males and 104 females), 51 Punjabi Muslims (29 males and 22 females) and 21 Afghans (15 males and 6 females) were screened for the presence of red cell glucose-6-phosphate dehydrogenase (G6PD) variants by a dye decolouration screening test and starch gel electrophoresis. The overall frequency of G6PD deficiency in males was found to be about 10%. 17 male G6PD-deficient samples were further investigated for the C-->T substitution at nucleotide (nt) 563 (the Mediterranean mutation) and the C-->T substitution at nt 1311 (the 'silent' allele) of the G6PD gene by PCR amplification followed by digestion with appropriate restriction enzymes. 10 of the 13 Pushtoon, 2 Punjabi and 1 Afghan males had the 563 mutations. Only 1 (Punjabi) out of 13 G6PD-deficient males with the 563 mutation had the silent mutation at nt 1311. The frequency of the silent mutation was found to be about 0.20 in the 60 Pushtoon and 19 Punjabi non-deficient males.

Base Sequence↗

PubMedDate not supplied

Effect of apolipoprotein E variants on plasma lipids and apolipoproteins in the Orang Asli ('aborigines') of Malaysia.

Members of the Semai group of Orang Asli ('aborigines') in peninsular Malaysia were examined for apolipoprotein E (apo E) variants in relation to plasma total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDLC), triglycerides (TG), apolipoprotein AI and apolipoprotein B (apo B). The e2 and e4 alleles were found to be higher than in most other groups as reported. The sample as a whole was normotriglyceridaemic (mean plasma TG, 1.5 mmol/l) and very markedly hypocholesterolaemic (mean plasma TC 1.7 mmol/l). The distribution of apo E variants was not related to any of the plasma lipids or apolipoprotein fractions using results from all subjects, but if a distinctly hypertriglyceridaemic sub-section was omitted (TG > 1.7 mmol/l) then apo E variants were determinants of plasma TC, LDLC, and apo B concentrations, the lower values of these being associated with the 2-2 and 2-3 genotypes, and the higher with 3-4, and 4-4.

Alleles↗

PubMedDate not supplied

Is p53 polymorphism maintained by natural selection?

We present here a new interesting feature of the human tumor suppressor gene p53: a very pronounced ethnic and clinal variation of polymorphic codon 72 alleles. The frequency of the A1 (Pro) allele showed a north-south cline from 17% in Swedish Saamis to 63% in African Blacks (Nigerians), and there was a significant (p < 0.001) correlation (r = 0.95) between the A2 frequency and latitude. In the Finnish and Swedish populations no significant differences were found with respect to the genotype and allele distributions in spontaneously aborted fetuses and liveborn children, which makes differential intrauterine selection unlikely. However, the ethnic and clinal variations suggest that the codon 72 polymorphism is balanced and maintained by natural selection.

Alleles↗

PubMedDate not supplied

Linkage disequilibrium between two loci (5' untranslated exon 1 and intron 5-DdeI) of the antithrombin III gene in three ethnic groups in Singapore.

The distribution of two common DNA polymorphisms (5' untranslated exon 1 and intron 5-DdeI) of the antithrombin III (ATIII) gene was studied in three ethnic groups in Singapore: 251 Chinese, 221 Dravidian Indians and 102 Malays. The polymorphisms were identified by the polymerase chain reaction and size fractionation in agarose gels. The 5' untranslated to exon 1 polymorphism is a length polymorphism while the intron 5 polymorphism is a restriction site (DdeI) polymorphism. The frequency of the short fragment (S) of the 5' to exon 1 length polymorphism of the ATIII gene was found to be 0.37 in the Chinese, 0.54 in the Malays and 0.65 in the Dravidian Indians. For the Chinese, this was significantly lower compared to the Caucasians and Indians (p < 0.0001) and the Malays (p < 0.01). On the other hand, the frequencies of DdeI+ did not vary significantly among these three populations (p > 0.05). The distribution of different genotypes at these two loci of the ATIII gene was in Hardy-Weinberg equilibrium in all three ethnic groups. A strong linkage disequilibrium between these two polymorphisms was observed in all the ethnic groups and the estimated correlation coefficient (delta) was 0.42 in the Chinese (p < 0.001), 0.61 in the Dravidian Indians (p < 0.001) and 0.43 in the Malays (p < 0.001). The frequencies of haplotype S+, L+ and L- were, respectively, 0.37, 0.40 and 0.23 in the Chinese, 0.65, 0.18 and 0.16 in the Dravidian Indians and 0.54, 0.37 and 0.09 in the Malays.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

PubMedDate not supplied

Five restriction fragment length polymorphisms of the APOA1-C3 gene and their influence on lipids and apolipoproteins in healthy Chinese.

The distribution of five restriction fragment length polymorphisms (RFLPs) of the APOA1-C3 gene cluster and their influence on serum lipids and apolipoprotein levels was investigated in 151 healthy Chinese of both sexes. The frequencies of the rare alleles at ApaI, BanI, XmnI (A1) and SstI (C3) sites were significantly different in the Chinese when compared to Caucasians as follows: ApaI: 0.25 vs. 0.42 (p < 0.02); BanI: 0.33 vs. 0.16 (p < 0.01); XmnI: X2, 0.30 vs. 0.14, and X3, 0.08 vs 0.05 (p = 0.001); SstI (C3): 0.23 vs. 0.12 (p = 0.011). The frequency of P2 (PstI) at 0.04 was similar to that in Caucasians (0.07). The distribution of the genotypes of all the RFLPs was in Hardy-Weinberg equilibrium in this population. A significant association of the SstI polymorphism of the C3 region with the serum high-density lipoprotein (HDL)-cholesterol level was observed in both men and women, the rarer allele (S2) being associated with higher levels (p < 0.05). 5.8% of the sample variance of the HDL-cholesterol level in this sample could be explained by the SstI polymorphism of the C3 region (F = 6.07, p = 0.003). The association of the SstI locus with serum HDL-cholesterol was stronger in males than in females (R2 = 13.8 and 6.7%, respectively). There was a similar trend of association of the serum apolipoprotein A-I level with the SstI polymorphism, though it did not reach statistical significance. There was no association between the levels of any of the lipid and apolipoproteins studied with RFLPs of the APOA1 gene.

Adult↗