Oral mucosal lesions in older people: relation to salivary secretion, systemic diseases and medications.

OBJECTIVES: To determine the prevalence of oral mucosal lesions in a sample of older Danish people and to investigate their associations with age, gender, systemic diseases, medications, xerostomia and salivary secretion. METHODS: A total of 668 community-dwelling individuals aged 65-95 years underwent a clinical examination, measurements of unstimulated and stimulated whole and labial salivary flow rates and an interview regarding xerostomia, general health, medication, tobacco and alcohol habits. RESULTS: Seventy-five per cent of all participants and 70% of the non-medicated ones had one or more oral mucosal lesions. The most prevalent lesions were lingual varicosities (28.3%), denture stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional keratosis (8.4%). Lesions were generally associated with smoking and xerostomia. Varicosities were more common in participants with systemic diseases and medication intake, particularly with cardiovascular diseases and agents. Fissured tongue and atrophic tongue were associated with female gender, xerostomia and low unstimulated whole and labial salivary secretion. Oral candidiasis was associated with older age; being male; current smoker; having >3 diseases, intake of medications and low salivary flow rates; and identified in relation to denture stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis. CONCLUSIONS: Oral mucosal lesions are prevalent in older Danish people and generally associated with changes in both local and systemic factors. Tongue lesions in particular appeared as indicators that may identify patients with specific need of oral intervention.

Polymorphic drug metabolizing CYP-enzymes--a pathogenic factor in oral lichen planus?

BACKGROUND: Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis. OBJECTIVES: To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism. METHODS: One hundred and twenty patients with OLP and 180 gender-matched controls without OLP were genotyped for CYP2C9, CYP2C19, and CYP2D6 alleles with absent or reduced function. RESULTS: The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females (P < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20-36%] than previously reported among Danes (19%; 95% CI 17-22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population (P = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans, which may result in molecular mimicry. CONCLUSION: It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.

Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment.

In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was under deep anaesthesia before 24.00 h on the day before oestrus. Pentobarbitone treatment of ovariectomized pigs resulted in a clear decrease in LH levels 40 min after a single i.v. dose.

PIP: Plasma luteinizing hormone (LH) and progesterone in the adult female pig during the estrous cycle, late pregnancy and lactation and after ovariectomy and pentobarbitone treatment was investigated. The preovulatory LH surge occurred in 7 of 8 animals between 0000 and 1200 hours on Day 0 of the estrous cycle (Day 1 of standing heat). Progesterone fell 8 days before estrus and reached its lowest value 5 days prior to the preovulatory LH peak. LH was low and showed only minor fluctuations during late pregnancy, parturition and lactation, while progesterone declined 4-5 days before parturition. Both were low during lactation. 3 weeks prior to parturition, LH increases were followed by progesterone increases. 4-12 days after weaning the animals came into estrus followed by a LH increase and later a progesterone increase. Ovariectomy during diestrus resulted in an increase (p less than .001) in LH for 35-39 days. Ovariectomy caused abortion when performed on Day 100 of pregnancy, followed by a rapid increase in LH. Around Day 115 normal parturition and lactation took place when animals were spayed on Day 112 of pregnancy. As long as lactation was maintained LH levels remained lower than before ovariectomy (p less than .01). After weaning a rapid increase in the normal postovariectomy LH pattern was seen. Less than 5 hours of 30-35 mg pentobarbitone anaesthesia/kg body weight during proestrus has no effect on the preovulatory LH increase. However, more than 6 hours inhibited the LH peak and ovulation when the animal was under deep anaesthesia before 2400 hours on the day before estrus. A clear decrease in LH 40 minutes after a single intravenous dose of pentobarbitone was seen in ovariectomized pigs.

Plasma oxytocin and steroid concentrations during late pregnancy, parturition and lactation in the miniature pig.

Plasma oxytocin concentrations were measured during late pregnancy, parturition and lactation in the miniature pig. Measurements were made of plasma oestradiol, oestrone and progesterone to determine whether there was any relationship between the concentrations of oxytocin and these steroids in the circulation. Plasma oxytocin concentrations were low or undetectable in late pregnancy. Rises of up to 68.8 mum./ml were seen at the time of delivery of the foetuses and at the expulsion of the placenta. The only steroid that seemed to relat to oxytocin release was progesterone. Oxytocin release was consistently seen when progesterone concentrations had fallen to below 10 ng/ml but no increase in concentration was observed while oestrone and oestradiol increased to their maximum concentrations of 3.86--11.6 and 0.43--0.70 ng/ml respectively. During lactation, when both oestrogen and progesterone concentrations were low, suckling caused the levels of oxytocin to increase to 7.4 muu./ml. These increases were greater during the first 2 weeks of lactation than later.

Plasma luteinizing hormone and testosterone in the adult male pig: 24 hour fluctuations and the effect of copulation.

Secretory patterns of LH and testosterone were characterized in the intact male miniature pig. All blood samples were taken from indwelling catheters. Hourly sampling was carried out over 24 h and during a morning period blood was collected for 2 h at 10 min intervals. No significant difference was detected in the plasma LH concentration on the basis of hourly sampling. Plasma testosterone was significantly (P less than 0-05) lower during the evening and night when compared with morning values. The second experiment was concerned with the pattern of plasma LH and testosterone concentrations before and after copulation. Blood sampling was performed at 10 min intervals. Plasma LH was significantly (P less than 0-001) raised for 30 min after copulation when compared with any 30 min period (0-120 min) before copulation. Plasma testosterone was not significantly altered for any 30 min period of the experiment (0-270 min). The data are interpreted as a possible mechanism for endocrine control of testicular function.

Behavior and heart rate of heifers housed in tether stanchions without straw.

The effect of tether housing without straw was studied in eight heifers over a 12-week period. Resting behavior was recorded in the first and the twelfth week and heart rate (HR) in the twelfth week and compared to that of eight control heifers kept in a group on deep straw. Tethered heifers changed body position from standing to lying and vice versa significantly less often, and frequency of lying intention movements prior to lying down was significantly increased in tethered heifers. Correspondingly, latency between first intention movement and actually lying down was markedly increased in tethered heifers. HR was significantly higher in tethered heifers in all situations studied. During the lying procedure, HR increased in all animals so that the difference between the two groups remained unchanged. The biggest difference between groups was measured during the first lying intention, when HR was 125.2 +/- 9.4 in tethered heifers and 76.8 +/- 6.1 in controls. The results indicate that lying down in tether stanchions is aversive to the heifers and avoided as much as possible.

Estrous cycle synchronization in dairy heifers with the prostaglandin analog alfaprostol (II).

Over a two year period, 276 dairy heifers (German Black Pied x Holstein Friesian) received one or two injections i.m. of 1.5 mg/100 kg body weight of the PGF analog alfaprostol. Only animals not showing heat after the first injection were treated twice, with the same dose, 11 days apart. Before treatment, 71% of the heifers were cycling regularly, 12% were cycling irregularly and 17% were not observed in heat prior to treatment. Animals in heat were inseminated once or twice, 18 to 24 h apart. In response to the first injection, 60.5% of all treated animals came into heat; 38% showed heat after the 2nd treatment. Three of the six non-responding animals were later diagnosed as freemartins. Heat was well synchronized. Twenty seven percent, 60% and 9% of all first inseminations occurred on days two, three and four after treatment (s), respectively; 65% of all heifers conceived from the first insemination. Pregnancy rates after one or two inseminations were 66.0% and 63.8%, respectively. At the second a.i., 45% of all animals had already ovulated. Pregnancy rates from first a.i. after one or two treatments with alfaprostol were 60.1% and 72.2%, respectively. Years had no influence on any of the parameters observed. Stage of cycle in which the first treatment occurred had a strong influence on the occurrence of heat and on conceptions as well. Of the animals treated between days 6 and 18% of their cycles, 92.6% responded with heat to the first treatment and 79% conceived. When animals were treated for the first time between days 19 and 5 of their cycles, only 28.8% came into heat and only 23.8% conceived. After the 2nd treatment, 71.2% of the latter group came into heat and 73.1% conceived.

An approach to successful freezing of demi-embryos derived from day-7 bovine embryos.

The developmental capacity of frozen/thawed bisected embryos (n = 33) derived from day-7 bovine embryos was investigated and compared to ordinary embryos after freezing and thawing (n = 28) and to freshly bisected embryos (n = 19). The freezing and thawing protocol was identical for ordinary and demi-embryos. The percentage of intact embryos classified as excellent, good, or poor after thawing was 92.9 and 96.3% for ordinary and demi-embryos, respectively. Pregnancy rates of 53.8 (8 15 ), 46.2 (6 13 ), and 47.5% (9 19 ) were obtained when frozen/thawed ordinary embryos and frozen/thawed demi-embryos classified as excellent or good and sealed with an additional zona pellucida from hatched pig blastocysts or freshly bisected embryos were transferred. One pair of identical twins resulted from the transfer of frozen/thawed demi-embryos sealed with an additional zona pellucida. Transfer of four frozen/thawed demi-embryos without an additional zona pellucida led to one pregnancy. In contrast, demi-embryos derived from frozen/thawed ordinary embryos (n = 8) as well as frozen/thawed demi-embryos classified as poor (n = 6) did not result in any pregnancies although two halves were transferred per recipient. It is concluded that sealing the punctured zona pellucida improves the developmental capacity of frozen/thawed demi-embryos derived from day-7 bovine embryos, and freezing demi-embryos is more efficient compared to the splitting of frozen/thawed ordinary embryos.

Uterine position and presentation of minipig-fetuses and their order and presentation at birth.

Uterine position and presentation of fetuses in 17 minipigs during pregnancy were compared with their order and presentation at birth. Fetuses from 1 or both uterine horns were marked between day 80 and day 105 of gestation by 1 or more transuterine injections of either a 2.5% solution of dianil blue (3 animals) or a radiopaque substance (14 animals). Roentgenograms of the newborn pigs, which were ear-notched immediately after birth, enabled making individual identification. Pigs seemed to be delivered randomly from the 2 uterine horns. They either followed a neighbor from the same horn (n = 42) or followed a pig from the contralateral horn (n = 52). Only in 3 dams did 1 uterine horn become empty before delivery from the other horn started. In 4 dams, 1 pig passed its neighbor from the same horn, thereby being born earlier than expected. Moreover, passing of pigs could have occurred and gone undetected in those dams from which the pigs of only 1 horn were marked. This passing might have taken place within the uterine body. From 18 of 95 pigs (19%) , the presentation at birth differed from the one observed at laparotomy.

[Physiologic reactions during the slaughter of cattle and sheep with and without stunning]. / Physiologische Reaktionen bei der Schlachtung von Rindern und Schafen mit und ohne Betäubung.

In a first trial the cortical activity of cattle and sheep was tested using only an electrocorticogram (ECoG). The results showed a shorter phase after sticking or the ritual slaughter cut respectively, until the ECoG disappears in stunned animals. However, considering the time between stunning and the cervical state, the interval until disappearance of the ECoG was prolonged in the stunned animals. The observed time differences, however, are only a tendency and not statistically confirmed. Insofar, concerning animal protection, the different slaughter methods could be regarded equivalent. A second trial was designed in a manner to allow a more exact interpretation of the ECoGs and was completed by measuring visually and somatosensorically evoked potentials. Additionally, in contrast to the first trial, only adult cattle were used here. The results revealed shorter intervals until disappearance of cortical activities when using captive-bolt stunning. Also the variance was much lower in this trial than after ritual slaughter. The mean of the time differences was relatively low (5.5 seconds). It was especially remarkable that after captivebolt stunning absolutely no evoked potentials could be registrated, whereas these potentials lasted for 77 seconds (somatosensorically evoked potentials) and 55 seconds respectively (visually evoked potentials) after the ritual slaughter cut. Thus, after ritual slaughter a nervous conduction was measured up to 126 seconds in the extreme cases. However, from the results obtained it can not be concluded whether or not pain sensitivity occurred in the animals.

[Maturational quality, adaptation reactions and clinical-chemical blood values in automatically milk-fed bred milk calves]. / Entwicklungsqualität, Adaptationsreaktionen und klinisch-chemische Blutwerte von am Tränkeautomaten aufgezogenen Milchrindkälbern.

Calves of the dairy herd were used for this investigation. Body weight and growth rate were measured at 4, 6, 10, 12 and 13 weeks of life and venous blood acid base status, gas content, creatinine, urea, total protein, Ca, Mg, P, Na, K, Cl, Fe and catecholamine content at 15 days and at 90 days of age as well. Changes of blood values were analyzed in connection with growth performance and with the blood values of calves at 15 days of age testing the individually different degrees of adaptation and development.

[Thyroid hormones in cesarean-delivered suckling calves after birth and in the first days of life--maternofetal relations and early postnatal adaptation reactions]. / Schilddrüsenhormone bei schnittentbundenen Saugkälbern nach der Geburt und in den ersten Lebenstagen--Maternofetale Beziehungen und frühe postnatale Adaptationsreaktionen.

Caesarean section delivered suckler calves and their dams from the mother cow herd were used for this investigation. Jugular venous blood samples taken immediately after delivery from the cow and the calf and in the calf at 24 hours and at 48 hours of postnatal age as well were analyzed for T4, FT4, T3 and FT3 by luminescence enzyme immunoassay. Strong correlation between the thyroid hormone values of the cow and those of the calf could be found. Higher thyroid hormone values were measured in calves increasing further at 24 hours of age and then decreasing a little at 48 hours of age with higher values in female than in male calves. A strong correlation existed between T3 and heart rate of the calves.

[Clinical chemical and hematological blood values and adaptation reactions in suckling calves in the first weeks of life]. / Klinisch-chemische und hämatologische Blutwerte und Anpassungsreaktionen bei Saugkälbern in den ersten Lebenswochen.

Suckler calves of the mother cow herd were used for this investigation. Body weight, growth rate and venous blood acid base status, gas content, creatinine, urea, lactate, total protein, albumin, Ca, Mg, Na, K and Cl were measured at 20, 60 and 90 days of postnatal life. Body weight and growth rate showed strong correlations with some blood values especially at 60 and 90 days of age meaning that adaptation is performed successful in some calves and incomplete in others. Disproportionate growth of body parts and the limited oxygen-carrying capacity below the oxygen needs of the tissues may cause the great lactate values in some calves of all age groups.

[Thyroid hormones in dairy calves after birth and in the first days of life. Amplitude of variation, maternal-fetal relationships and reaction patterns specific to the individual]. / Schilddrüsenhormone bei Milchrindkälbern nach ber Geburt und in den ersten Lebenstagen. Variationsbreite, maternofetale Beziehungen und individualspezifische Reaktionsformen.

Dairy calves and their dams from the dairy herd of the institute were used for this investigation. Calvings were watch carefully and jugular venous blood samples taken immediately after delivery from the cow and the calf and in the calf at 24 hours and at 48 hours of postnatal age as well were analyzed for T4, FT4, T3 and FT3 by luminescence enzyme immunoassay (LEIA). Higher thyroid values in calves than in their dams could be found increasing short after birth and reaching their highest level within 24 hours of postnatal life. The individual thyroid hormone values at birth and at 24 hours and at 48 hours of age are well correlated meaning the changes during the first days are specific for each calf. Strong correlation between the thyroid hormone values of the cows and those of the calves could be found. Mean values of thyroid hormones were significantly higher in female than in male calves all time but not different in the dams of these calves.

Associations between oral and ocular dryness, labial and whole salivary flow rates, systemic diseases and medications in a sample of older people.

OBJECTIVE: To investigate the associations between age, gender, systemic diseases, medications, labial and whole salivary flow rates and oral and ocular dryness in older people. METHODS: Symptoms of oral and ocular dryness, systemic diseases, medications (coded according to the Anatomical therapeutic chemical (ATC) classification system), tobacco and alcohol consumption were registered, and unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS) whole salivary flow rates were measured in 668 randomly selected community-dwelling elderly aged 65-95. RESULTS: Presence of oral (12%) and ocular (11%) dryness was positively correlated. Oral dryness was associated with low UWS, SWS and LS, and ocular dryness with low UWS and SWS. Oral and ocular dryness was related to female gender, but not to age. Only four persons in the healthy and nonmedicated subgroups reported oral and ocular dryness. The numbers of diseases and medications were higher in the older age groups and associated with oral and ocular dryness, low UWS, SWS and LS. On average, women were slightly older, reported more oral and ocular dryness and had lower UWS, SWS, LS and higher numbers of diseases and medications. High prevalence and odds ratios for oral dryness were associated with metabolic, respiratory and neurological diseases and intake of thyroid hormones, respiratory agents (primarily glucocorticoids), psycholeptics and/or psychoanaleptics, antineoplastics, proton pump inhibitors, antidiabetics, loop diuretics, antispasmodics, quinine and bisphosphonates. Ocular dryness was especially associated with neurological diseases and intake of psycholeptics and/or psychoanaleptics. Intake of magnesium hydroxide, antithrombotics, cardiac agents, thiazides, beta-blockers, calcium channel blockers, ACE inhibitors/angiotensin II antagonists, statins, glucosamine, paracetamol/opioids, ophthalmologicals and certain combination therapies was related to oral and ocular dryness. CONCLUSIONS: In older people, oral and ocular dryness are associated with low salivary flow rates, specific as well as high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. New detailed information concerning associations between medications and oral and ocular dryness has been obtained using the ATC classification system.