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PubMed2003

Peripartum cortisol levels and mother-infant interactions in Japanese macaques.

As evidence accumulates regarding the influence of hormones and stress-related conditions on maternal behavior, it becomes critical to better understand the relationship between physiological stress and the ability to cope with infants. Eight Japanese macaque females were observed 3 hr per week during the first 12 weeks after parturition; fecal samples were collected twice a week from each mother, starting 4 weeks before parturition and ending 4 weeks after parturition. Time spent in contact, maternal responsiveness, latency of response, and maternal rejection were measured and correlated with peripartum excreted cortisol and estradiol metabolite levels. Two indices of peripartum hormonal status were also tested against behavior: the postpartum stress index, and the postpartum cortisol/prepartum estradiol ratio (F/E). Postpartum cortisol levels showed a positive correlation with maternal rejection. The cortisol/estradiol ratio was positively correlated with rejection and latency of response, and negatively correlated with maternal responsiveness. Prepartum cortisol levels and the postpartum stress index did not correlate with any aspect of maternal behavior. Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis activity per se is not enough to predict the quality of interaction between mother and infant. Only when cortisol is high relative to estradiol could it be symptomatic of a possible negative feedback response involving stress, adrenal activity, and the ability of mothers to cope with the additional problems imposed by newborns.

Animals↗
PubMed2004

Patterns of behavior across reproductive states of free-ranging female black-handed spider monkeys (Ateles geoffroyi).

Reports on the behavior of spider monkeys (genus Ateles) describe a suite of 5-6 behaviors that are indicative of an estrous female. This study presents hormonal data as an independent measure of reproductive state to determine if these behaviors are associated with any particular reproductive state or stage of the ovarian cycle. Fecal samples collected from 6 free-ranging female black-handed spider monkeys (Ateles geoffroyi) over the course of 11 months were assayed for estrogen (E1C) and progesterone (PdG) metabolites, using an enzyme immunoassay. Behavioral data collected from the same females were analyzed for patterns associated with different reproductive states. A more detailed analysis of behavioral data associated with reproductively cycling periods determined whether each behavior clustered with copulations or a particular phase in the ovarian cycle. Observations of place-sniffing were more frequent for 4 of 5 females when reproductively cycling. Of all copulations observed, 80% occurred when the female participant was reproductively cycling. In addition, the rates of self-clitoral hold and self-clitoral rub behaviors were significantly higher for 2 of 4 and 4 of 5 of females, respectively, when reproductively cycling. No behavior consistently occurred in association with copulations or with any particular phase in the ovarian cycle. Results from this study suggest that the behaviors tested in this paper can provide some information regarding female spider monkey reproductive state (whether or not she is reproductively cycling), but that they are not indicators of estrus in female spider monkeys.

Animals↗
PubMed2005

Paternity and kinship patterns in polyandrous moustached tamarins (Saguinus mystax).

We studied patterns of genetic relatedness and paternity in moustached tamarins, small Neotropical primates living in groups of 1-4 adult males and 1-4 adult females. Generally only one female per group breeds, mating with more than one male. Twin birth are the norm. In order to examine the genetic consequences of this mating pattern, DNA was extracted from fecal samples collected from two principal and six neighboring groups. DNA was characterized at twelve microsatellite loci (average: seven alleles/locus). We addressed the following questions: Do all adult males have mating access to the reproductive female of the group? How is paternity distributed across males in a group? Can polyandrous mating lead to multiple paternity? Are nonparental animals more closely related to the breeders than to the population mean? And, are mating partners unrelated? Breeding females mated with all nonrelated males. In at least one group the father of the older offspring did not sire the youngest infant although he was still resident in the group. We also found evidence for multiple paternity in a supposed twin pair. Yet, within each group the majority (67-100%) of infants had the same father, suggesting reproductive skew. Relatedness within groups was generally high (average R = 0.31), although both nonrelated males and females occurred, i.e., immigrations of both sexes are possible. Mating partners were never found to be related, hence inbreeding seems to be uncommon. The results suggest that while the social mating system is polyandry, paternity is often monopolized by a single male per group.

Animals↗
PubMedDate not supplied

HPLC determination of benzthiazide in biologic material.

An assay was developed for benzthiazide in plasma, urine and feces, using high performance liquid chromatography (HPLC). A reverse-phase column was employed, with quantitation af 280 nm, using polythiazide as an internal standard. In three of four human subjects who received a 50 mg benzthiazide tablet the plasma concentrations were below the 10 ng ml-1 sensitivity limit of the assay, and the urinary recovery averaged less than one per cent of the dose. One subject received a 50 mg dose as both a tablet and a solution; the urinary recoveries for these two doses were 1.7 and 10.4 per cent, respectively. Fecal samples, obtained from two subjects who received 50 mg tablets, were estimated to contain approximately 80 per cent of the administered dose.

Adult↗
PubMed1995

The effect of the fat content of food on the pharmacokinetics and pharmacodynamics of SDZ FOX 988, an antidiabetic agent, in the dog.

SDZ FOX 988 (FOX 988) is being developed for the treatment of type II diabetes. The objective of this study was to examine the effect of the fat content of food on the pharmacokinetics and pharmacodynamics of FOX 988 following oral administration in the dog. In a randomized, cross-over design, four dogs received a single 10 mg kg-1 dose of 14C-FOX 988 suspension concomitantly with food containing 10% fat or 40% fat, or with the 10% fat food at 4 h post-dose. Serial blood, urine, and fecal samples were collected for 96 h and analyzed for total radioactivity. Blood concentrations of 53-450, the active metabolite of FOX 988, were also determined. Serum concentrations of beta-hydroxybutyrate and glucose, pharmacological markers for the antidiabetic effects, were measured serially for 24 h after dosing. The animals receiving the low-fat meal at dosing and at 4 h post-dose exhibited similar extents of absorption, as shown by similar AUC values and urinary radioactivity recovery. Administration of the high-fat meal at dosing significantly enhanced the absorption of FOX 988 and resulted in high blood concentrations of 53-450. However, no significant differences in the pharmacological activity of the drug were observed among the three treatments.

3-Hydroxybutyric Acid↗
PubMed1995

The effect of food on the absorption of 14C-SDZ FOX 988, an antidiabetic agent, in healthy human volunteers.

The objective of this study is to examine the effect of food on oral absorption of SDZ FOX 988 (FOX 988), an antidiabetic agent, and circulating levels of its active metabolite, SDZ 53-450 (53-450). Sixteen normal volunteers received a single 10 mg dose of 14C-FOX 988, either as gelatin capsules or in a suspension (0.5% CMC). For subjects receiving each formulation, four subjects received a meal, consisting of 50% fat by calories, immediately following dosing, while the other four received the same meal at 2 h post-dose. Serial blood, urine, and fecal samples were collected for 120 h and analyzed for total radioactivity. Blood concentrations of 53-450 were analyzed using an HPLC-UV method. Concomitant administration with food increased the extent of FOX 988 absorption from either suspension or capsule, as shown by an increase in AUC and in urinary recovery of radioactivity. Blood concentrations of 53-450 were only detected in subjects receiving food at dosing. No difference in absorption was observed between the capsule and the suspension. Results from this study showed that oral absorption of FOX 988 is enhanced by co-administration of food in normal volunteers.

Absorption↗
PubMed2004

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers.

Palonosetron (Aloxi(R), Onicit(R)) is a potent, single stereoisomeric 5-HT(3) receptor antagonist developed to prevent chemotherapy-induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [(14)C]-palonosetron (10 microg/kg, 0.8 microCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half-life of 37 h. Approximately 83% of the dose was recovered in urine ( approximately 40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not beta-glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body.

Adult↗
PubMed1977

Diuretic effect and metabolism of bumetanide in man.

Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.

Adult↗
PubMed1985

Tolerance and percutaneous absorption of topically applied arildone.

Arildone, an investigational antiviral agent, was compared to both its vanishing cream and 90% dimethyl sulfoxide (DMSO) solution vehicles to determine cutaneous and systemic tolerance as well as percutaneous absorption. In separate studies, immunosuppressed patients randomly received either arildone in vanishing cream (study 1), arildone in DMSO solution (study 2), or the vehicles without arildone. Test formulations were applied to the same area of one forearm four times daily for seven days. Blood, urine, and fecal samples were collected on days 1, 4, and 7, and patients were observed daily. Arildone was sporadically detected in biologic specimens suggesting limited percutaneous absorption. Unexpectedly, DMSO did not appear to enhance absorption of the drug. No clinical or laboratory evidence of systemic intolerance was observed for any preparation. While cutaneous tolerance was excellent for the vanishing cream preparations, the DMSO preparations were associated with a high (90%) incidence of erythematous reactions.

Administration, Topical↗
PubMed1995

Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers.

Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract. Systemic absorption is not required for its efficacy, but knowledge of the extent of its systemic absorption is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening was carried out by monitoring plasma concentrations of unchanged orlistat in 25 phase 1 studies (including two mass balance studies) in normal and obese healthy volunteers. The results of these studies indicate an extremely low degree of systemic absorption for orlistat when administered with a hypocaloric, well-balanced diet with 20% to 30% of calories derived from fat (50-80 gm). To further characterize the pharmacokinetics and excretion pathways of orlistat, two mass balance studies using 14C-labeled orlistat were conducted. After oral dosing of radiolabeled orlistat with a fatty meal (28-30 gm fat), almost the entire dose was recovered from fecal samples; little was found in plasma and urine. It is concluded that systemic absorption of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.

Clinical Trials, Phase I as Topic↗
PubMed1988

Increased intestinal absorption of calcium in young and adult X-linked hypophosphatemic mice after the administration of 1,25-dihydroxyvitamin D3.

We have reported that X-linked hypophosphatemic (Hyp) and normal mice respond equally to the administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] with uptake of 45Ca from an oral test meal as judged by the isotope remaining in the fecal samples. To determine whether this was due to specific stimulation of calcium absorption, as opposed to changes in calcium secretion or transit time, 1,25(OH)2D3 was administered to 4-week-old (young) and 13-week-old (adult) normal and Hyp mice at a dose of 0.12 micrograms/kg per day by continual infusion from an Alzet minipump. After 3 days of infusion, absorption of 45Ca from the isolated duodenum was measured in situ. Malabsorption of calcium was shown in vehicle-treated 4-week-old Hyp mice by significantly more 45Ca remaining in the intestinal segment and by significantly reduced plasma levels and reduced skeletal levels of 45Ca. Treatment of the young mice, both normal and Hyp, with 1,25(OH)2D3 resulted in increased absorption of 45Ca, increased plasma 45Ca, and increased incorporation of 45Ca into the femur. The young Hyp mice treated with 1,25(OH)2D3 showed a significant increase in femoral ash weight. At 13 weeks of age both normal and Hyp vehicle-treated mice showed equivalent absorption of calcium, and both responded to 1,25(OH)2D3 administration with enhanced calcium absorption. At both ages plasma phosphate rose in only the Hyp mice treated with 1,25(OH)2D3, whereas plasma and urine calcium were increased in only the hormone-treated normal mice. In conclusion, 1,25(OH)2D3 stimulates the absorption of calcium in the isolated duodenum of the young Hyp mouse with equal potency to that of young normal mice.

Aging↗
PubMed2001

Nucleotide sequence analysis and development of consensus primers of RT-PCR for detection of Norwalk-like viruses prevailing in Japan.

A total of 177 different nucleotide sequences of the RNA polymerase region of Norwalk-like viruses (NLVs) genomes, collected via a nation-wide survey project in Japan between 1989 and 1998, were examined by reverse transcription-polymerase chain reaction (RT-PCR) employing various primer pairs. The nucleotide sequences of different strains showed great diversity, with a range of 57 to 100% identities among strains. The strains could be classified into five clusters: Norwalk (NV), Snow Mountain agent/Bristol virus (SMA/BV), Toronto virus/Mexico virus (TV/MX), and Japan specific cluster 1 and 2 (JP-1 and JP-2). Within each cluster there is greater than 85% identity of amino acid sequence (more than 75% identity of nucleotide sequences), based on sequence homology analysis. We believe that two of the five clusters, JP-1and JP-2, define new specific clusters found in Japan according to phylogenetic and pair-wise comparison studies. An RT-PCR procedure was designed using new consensus primer pairs, P1/P2, P1/P3, and Y1/Y2 based on multiple alignment of collected nucleotide sequences, that are expected to detect nearly all NLVs prevailing in Japan. The usefulness of the primers was tested by ten different laboratories in Japan using a panel of ten fecal samples containing different virus strains. The identification of these primer pairs will facilitate routine diagnosis of NLV infection by RT-PCR and offers the potential for their direct detection in food and environmental samples.

Caliciviridae Infections↗
PubMed1988

Use of polyclonal and monoclonal antibodies and analysis of viral RNA in the detection of unusual group A human rotaviruses.

Immuno-enzymatic assay employing monoclonal antibodies and viral RNA analysis by gel electrophoresis were used to classify human group A rotaviruses (HRV) into subgroups I and II. Of 249 fecal samples positive for group A rotaviruses, 29 (11%) belonged to subgroup I and 215 (85%) were identified as subgroup II. Two samples (Ro-302 and Ro-500) contained mixed infections of the two subgroups. Three isolates belonged to neither one of the two subgroups, but they did not yield enough viral RNA to allow their classification. One subgroup I isolate (Ro-1845) contained components typical of subgroup II viruses in that it was identical to serotype 3 and yielded RNA with fast-moving 10th and 11th segments. After growth in culture, the two mixed infections yielded subgroup II viruses, which were identified as serotype 1. The three unclassified isolates grew poorly in culture and could not be further analyzed. The subgroup I isolate (Ro-1845) grew well in culture and yielded virus similar to the original one.

Antibodies↗
PubMed2001

Molecular epidemiology of calicivirus infections in Norway.

The national reference laboratory for calicivirus diagnostics monitors the epidemiology of calicivirus infections in Norway. During winter 1998-1999, 406 fecal samples were received from patients with suspected calicivirus infection. Of these, 76 (19%) were calicivirus positive by a nested reverse transcription-polymerase chain reaction. A number of alternative PCR designs were employed to disclose false negatives, but none were found. One half of the PCR positive samples were sequenced in order to investigate whether various cases represented the same outbreak, and to what extent a single or multiple subtypes were responsible for the morbidity during this season. The sequence data revealed that the majority of cases represented a genotype related to the Lordsdale strain, whereas the remaining cases seemed more sporadic. Most often, samples from particular outbreaks were highly homogeneous. However, in a few cases, samples connected with the same outbreak proved to contain epidemiologically independent strains.

Caliciviridae↗
PubMed2005

An outbreak of hepatitis A among homeless drug users in Rotterdam, The Netherlands.

From the end of January to mid-June 2004 (weeks 5-24) a hepatitis A virus (HAV) outbreak occurred among a homeless and drug user community in Rotterdam, The Netherlands. To prevent further spread of the virus within this group and to the general population, the Municipal Health Service of Rotterdam organized a mass vaccination campaign during which 83% (1,515/1,800) of the homeless people were vaccinated. As part of a national HAV typing study, blood and/or fecal samples of 30 Rotterdam HAV IgM+ patients who fell ill during the period of 1 September 2003-1 December 2004 were tested. The tests included RT-PCR and sequencing at the VP3-VP1 and VP1-P2a regions of the HAV genome. It was found that 12 homeless people, one family member of a homeless person and two people without a known risk were infected with a unique subtype 3a strain. Four of the homeless patients became ill after vaccination and were probably infected at the time. This study shows that Dutch homeless people and drug users involved in HAV outbreaks should be offered HAV vaccine actively to prevent further spread of the infection. Furthermore, it was shown by molecular techniques that the unique subtype 3a strain was not found before the Rotterdam outbreak or afterwards, indicating that the mass vaccination campaign was successful.

Disease Outbreaks↗
PubMed2006

Rotavirus diarrhea in children and adults in a southern city of Brazil in 2003: distribution of G/P types and finding of a rare G12 strain.

Between May and August in 2003, a total of 251 fecal samples were collected from children and adults with diarrhea (5 inpatients and 246 outpatients) at a private hospital in the city of Ponta Grossa, the state of Paraná, Brazil. Group A rotavirus was detected in 71 of 251 (28.3%) specimens: 55 (77.5%) from children under 5 years of age and 16 (22.5%) from individuals aged 6-72 years. All 71 strains exhibited a "long" RNA pattern when analyzed by PAGE. Sixty-one positive samples that yielded enough RNA were submitted to PCR genotyping. The most frequent G/P genotype combination detected was G1P[8] (86.9%; 53/61) followed by G9P[8] (3.3%; 2/61) and G12P[9] (1.6%; 1/61). Rotaviruses with G2, G3, G4, P[4], or P[6] specificity were not detected. For three strains (4.9%) bearing G1 genotype, the VP4 specificity could no be determined, and two specimens (3.3%) remained G/P non-typeable. One rotavirus strain (HC91) bearing G12P[9] genotype with a "long" electropherotype was isolated from an 11-month-old boy with diarrhea for the first time in Brazil. The cell-culture grown HC91 strain was shown to belong to serotype G12 by neutralization.

Adolescent↗
PubMed2006

Identification of the first strain of swine hepatitis E virus in South America and prevalence of anti-HEV antibodies in swine in Argentina.

In Argentina, a country considered non-endemic for hepatitis E virus (HEV) infection, serologic evidence of HEV infection has been observed in different human population groups. In other countries, a high degree of genetic relatedness has been observed between human and swine HEV genotype 3 sequences, suggesting zoonosis as one probable route of infection. This is the first identification of swine HEV in South America. HEV RNA was detected and sequenced in the ORF 1 and ORF 2 regions from swine fecal samples from a herd located in Pergamino, in the province of Buenos Aires. These strains all group into genotype 3 and exhibit a close relationship to two novel HEV variants previously identified in Argentina from sporadic acute cases of non-A to -C hepatitis in humans. In addition, using a modified commercial ELISA, the presence of anti-HEV antibodies was surveyed in five provinces across the country and all five showed a prevalence of HEV antibodies, ranging from 4% to 58%. The results suggest that swine could be an important reservoir for virus transmission in Argentina as has been suggested for other non-endemic areas. The Argentine human strains and swine strain described in this article seem to be closely related to a human Austrian strain, suggesting a potential European origin of HEV infection in these cases.

Animals↗
PubMed2025

Clinical Impact and Genetic Analysis of Enteric Viruses Associated With Acute Gastroenteritis in Greater Accra, Ghana: A Comprehensive Study of Five Viruses.

Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Humans↗