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C Roth

Publications and source records attributed to C Roth.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Outbreak of Ebola hemorrhagic fever in the Republic of the Congo, 2003: a new strategy?].

This article describes the last Ebola haemorrhagic fever (EHF) outbreak that occurred in the Cuvette Ouest Region of the Republic of Congo from January to April 2003. Epidemiological study demonstrated that the first patient, in whom diagnosis was made retrospectively, became ill on December 25, 2002. Subsequently until May 7, 2003, a total of 143 cases were recorded in the Mbomo and Kéllé health districts including 129 fatalities. Thirteen cases were laboratory confirmed and 130 were epidemiologically linked. Fifty-three percent of patients were male. Age ranged form 5 days to 80 years. Transmission involved direct contact with an infected person especially within families. Epidemiological data traced introduction of Ebola virus into the population to three primary cases mainly involving hunters. In all three cases development of the disease followed contact with non-human primates (gorillas) and other mammals (antelope) that had either been killed or found dead. Three health care workers were infected during the epidemic but nosocomial transmission played a minor role in the epidemic. On June 5, the Minister of Health and Population of the Congo Republic officially declared that the outbreak of EHF was over in the Cuvette Ouest Region. The last case was recorded on April 22 in the small village of Ndjoukou.

Adolescent↗
PubMed2002

Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones.

Interleukin-11 (IL-11) is a stromal cell-derived cytokine that can enhance osteoclast formation and stimulate bone resorption. In the present study, the characteristics of the resorptive effect of IL-11 in mouse calvarial bones were investigated. Both recombinant mouse IL-11 and human IL-11 caused concentration- and time-dependent stimulations of (45)Ca release from prelabeled mouse calvariae. Half-maximal responses were obtained at 0.7 ng/mL (approximately 40 pmol/L). Mouse and human IL-11 also stimulated release of (3)H from [(3)H]-proline-labeled bones. The magnitude of the (45)Ca and (3)H release (1.4-1.6-fold) caused by a maximally effective concentration of IL-11 was less than the stimulation (2.5-4.0-fold) elicited by a maximum concentration of parathyroid hormone (PTH). Release of (45)Ca by IL-11 was unaffected by the mitotic inhibitors, hydroxyurea and aphidicolin. In addition to resorption of bone, IL-11 caused a small (1.5-2.0-fold) enhancement of prostaglandin E(2) (PGE(2)) biosynthesis in calvariae, but had no effect on the mRNA expression of cyclooxygenase-1 and -2, or cytosolic phospholipase A(2). Indomethacin and flurbiprofen abolished the formation of PGE(2) and partially reduced (45)Ca release stimulated by IL-11. When either mouse interleukin-4 (IL-4) or interleukin-13 (IL-13) was added to calvariae treated with IL-11, (45)Ca release was inhibited. Resorption caused by IL-11 was also inhibited by both anti-mouse glycoprotein 130 (gp130) and an antibody neutralizing IL-11, but these agents had no effect on (45)Ca release caused by PTH or 1,25(OH)(2)vitamin D(3) (D(3)). Real-time, quantitative polymerase chain reaction (PCR) analysis (TaqMan PCR) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that IL-11 caused concentration-dependent enhancements of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) mRNA, without affecting the mRNA expression of RANK. Mouse RANKL stimulated (45)Ca release in the calvarial bones. The stimulatory effects of RANKL and IL-11 were inhibited by mouse OPG. These data demonstrate that IL-11 stimulates osteoclastic resorption in mouse calvariae by mechanisms that are independent of cell proliferation; partially dependent on prostaglandin biosynthesis; sensitive to inhibition by IL-4, IL-13, and OPG; and associated with enhanced expression of RANKL and OPG. In addition, IL-11 was not found to play an essential role in resorption stimulated by other calciotropic agents in calvariae.

Animals↗
PubMed2002

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

OBJECTIVE: In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. DESIGN AND PATIENTS: Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. RESULTS: The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. CONCLUSIONS: Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients' families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.

Adolescent↗
PubMed2002

Bone-resorbing activity from cholesterol-exposed macrophages due to enhanced expression of interleukin-1alpha.

The presence of cholesterol crystals, macrophages, and foreign giant cells has been associated with impaired bone healing of periapical lesions. Therefore, we investigated whether macrophages exposed to cholesterol crystals can release factors changing the activity of bone-resorbing osteoclasts. Mouse peritoneal macrophages treated with cholesterol crystals in vitro produced factor(s) that stimulated the release of 45Ca and 3H from mouse calvariae pre-labeled with 45Ca(CaCl2) or [3H]-proline, respectively. No bone-resorbing activity was released by epithelial cells, fibroblasts, or osteoblasts exposed to cholesterol crystals. Interleukin-1 receptor antagonist protein and antiserum neutralizing mouse interleukin-1alpha (IL-1alpha) inhibited 45Ca release induced by cholesterol-activated macrophages. The addition of cholesterol to the macrophages augmented the release of IL-1alpha protein and the expression of IL-1alpha mRNA. These findings indicate that frustrated phagocytosis by macrophages exposed to cholesterol crystals results in release of factors stimulating osteoclastic bone resorption, primarily due to increased transcription of the IL-1alpha gene.

Animals↗
PubMed2002

Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome.

Testolactone is used to treat conditions with excessive estrogen synthesis, e.g. gonadotropin-independent precocious puberty in McCune-Albright syndrome (MAS). Unfortunately, daily treatment with testolactone requires 3 to 4 doses (10-20 tablets) and even at these doses it is sometimes ineffective. We treated a patient with MAS (café-au-lait spots; thelarche at age 2- 6/12 yr; menarche at 5- 5/12 yr; accelerated bone age [BA 10 yr]) with the highly selective aromatase inhibitor anastrozole (1 mg once per day). Tamoxifen 1 mg/kg per day was added for 1 year but was discontinued when an ovarian cyst developed with markedly elevated estradiol levels. Estradiol levels returned to normal after resuming anastrozole-only treatment and accelerated BA progressed only 6 months during 2 1/2 years of treatment. The potent estrogen suppressive action and simple dosage regimen of anastrozole suggest it may be advantageous compared to other aromatase inhibitors such as testolactone or anti-estrogens.

Anastrozole↗
PubMed2001

Tumor cell differentiation by butyrate and environmental stress.

The present study shows that stress signaling plays a role in differentiation of K562, PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differentiation in K562, PANC1, and HT29 cells can be inhibited by SB203580, a specific inhibitor of p38 stress activated protein kinase. (2) Heat shock and hyperosmolarity increase expression of differentiation markers in K562, HT29, HL60 and in K562, PANC1, and HT29 cells, respectively. (3) Conversely, environmental stress induced differentiation in K562, HT29, and PANC1 cells can be inhibited by SB203580 and quercetin, a compound with heat shock pathway inhibiting activity. (4) Butyrate and environmental stress enhance either additively or synergistically differentiation of K562, HT29, PANC1 or HL60 cells, respectively. Stress signaling pathways might be an interesting pharmacologic target for differentiation therapy of malignant disease.

Butyrates↗
PubMed2001

[The iodine supply of newborns. Comparison of iodine absorption and iodine excretion of mother and child].

BACKGROUND: Since 1989 the use of iodized salt has been allowed in Germany, additional supplementation with iodide tablets has been recommended during pregnancy and lactation. This study was undertaken to clarify whether the iodine intake of neonates and young infants improved since then. PATIENTS AND METHODS: In the first part of the study the urinary iodine excretion of 52 newborns and their mothers in 1998 was compared to data of similar studies 1983 in the area of Göttingen and 1982 in the areas of Heidelberg and Rothenburg, Germany. All these are geographically low-iodine areas. In the second part the iodine supply of infants in 1998-1999 under feeding with mother's milk or formulas in 1998 and 1999 was obtained by measuring iodide concentrations in urine and milk using a high pressure liquid chromatography (HPLC) method. RESULTS: 45% of pregnant women were without iodide supplementation in 1998. In 1998 the median urinary iodide concentration during the first week of life was 4.3 micrograms/dl, which was more than twice that found in 1983 (1.75 micrograms/dl). Infants feeding by mother's milk without maternal iodine supplementation or by semi-elementary diet had the lowest urinary iodine excretion, whereas significantly higher values were measured when feeding formulas for term or preterm infants. CONCLUSIONS: The iodine intake of newborns has markedly improved during 15 years. The WHO criterias for adequate iodine supply (TSH < 5 microU/ml and urinary iodine >/ = 10 micrograms/dl) were only partly fulfilled in Göttingen indicating that a mild iodine deficiency still exists with the risk of iodine deficiency disorders.

Bottle Feeding↗
PubMed2001

Reduction of gamma-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats.

Brain irradiation in prepubertal children with malignomas can cause precocious puberty. A selective cranial cobalt (Co(60))-irradiation technique has been developed in rats. In two experiments early juvenile (13-15 days old) female rats received a single dose of 5 Gy or sham irradiation. At pubertal age (post-natal days 33-34) irradiated rats had higher serum estradiol and luteinizing hormone levels. In experiment 1 irradiated rats had higher gonadotropin releasing-hormone (GnRH) mRNA levels in the preoptic area compared to controls (P<0.05). In experiment 2 the release rates of gamma-aminobutyric acid (GABA) in vitro from preoptic mediobasal hypothalamic areas of irradiated rats were significantly reduced after stimulation with the GABA(A) receptor agonist muscimol (maximum values 4607+/-804 vs. 7399+/-1048 pM in controls, mean+/-SEM, P<0.05). Radiation induced central precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to premature activation of the GnRH-pulse generator.

Animals↗
PubMed2001

Identification of committed NK cell progenitors in adult murine bone marrow.

Natural killer (NK) cells play important roles in innate immunity by lysing tumor and virally infected cells and by producing cytokines including interferon-gamma. While NK cell progenitors have been described in the fetal thymus, NK cell generation from hematopoietic stem cells (HSC) in the bone marrow (BM) occurs throughout life, and in athymic mice and humans. Interleukin (IL)-15 promotes NK development in vitro and is essential for the generation of normal numbers of NK cells in vivo. By characterizing BM cells expressing IL-15 receptor components, we found marked heterogeneity within the IL-2 receptor beta chain(+) (CD122(+)) subset, which included cells uniquely committed to the NK lineage. These CD122(+) NK cell precursors (NKP) are negative for markers used to identify mature NK cells, including NK1.1, DX5 and members of Ly-49 family, and fail to demonstrate natural cytotoxicity against susceptible target cells. In vitro culture of NKP generates mature lytic NK1.1(+) cells at high frequencies, while they do not give rise to T, B, myeloid or erythroid cells under appropriate conditions. NKP lack transcripts associated with early B and T cell differentiation (pTalpha, lambda5 and CD3epsilon), but express a group of genes (IL-15Ralpha, Id2, GATA-3 and Ets-1) and the 2B4 marker, which may define NK cell commitment. We propose that NKP represent the earliest adult BM precursor uniquely restricted to the NK cell lineage.

Animals↗
PubMed2001

Continuous measurement of drying rate of crystalline and amorphous systems during freeze-drying using an in situ microbalance technique.

The use of a novel microbalance (Christ) technique to monitor continuously the weight loss of a vial standing on a shelf of a freeze-dryer has been investigated. The drying rates of the following aqueous solutions were measured during the primary drying phase of a complete freeze-drying cycle: sucrose (75 mg/mL, 2.5-mL fill volume), sucrose and phenylalanine (1:0.2 by weight, 75 mg/mL, 2.5-mL fill volume), and mannitol (75mg/mL, 2.5-mL fill volume). The microbalance yields the cumulative water loss, m(cu) in grams, and the momentary drying rate, Deltam(cu)/Deltat in mg/10 min, of the frozen cake. The momentary drying rate curves were especially useful for examining how Deltam(cu)/Deltat changes with time during primary drying. Initially, Deltam(cu)/Deltat rises to a sharp maximum and then decreases in a fashion depending on shelf temperature, chamber pressure, and the nature of the substance being dried. Different drying behavior was observed for the sucrose and sucrose/phenylalanine systems, which was attributed to the presence of crystalline phenylalanine in the amorphous sucrose. At low shelf-temperature (-24 degrees C) the crystalline mannitol showed lower Deltam(cu)/Deltat than with either sucrose or sucrose/phenylalanine. The balance could also detect differences in Deltam(cu)/Deltat when using different freezing protocols. "Slow" and "moderate" freezing protocols gave similar drying behavior, but "rapid" freezing in liquid nitrogen produced greatly altered drying rate and internal cake morphology. The balance also could be used to detect the endpoint of primary drying. Different endpoint criteria and their influence on final dried cake properties were examined.

Crystallization↗
PubMed2001

Cisplatin nephrotoxicity in children after continuous 72-h and 3x1-h infusions.

Little is known about the association between the rate of cisplatin administration and the severity of cisplatin-induced renal damage in children. The purpose of this study was to compare severity and reversibility of renal damage in children after continuous and repetitive bolus administration of cisplatin and to correlate these data with pharmacokinetic parameters. Study subjects included six children (ten courses) receiving cisplatin as 1-h bolus infusions on three consecutive days (3x40 mg/m2) and four children (eight courses) receiving 72-h continuous infusions (120 mg/m2). In all courses, signs of glomerular and tubular damage were seen, as evidenced by elevated urinary excretion of alpha1-microglobulin, albumin and N-acetyl-beta-D-glucosaminidase and decreased glomerular filtration rate (GFR). Comparing the two infusion regimens, the 1-h bolus administration of cisplatin was followed by significantly higher peak free platinum concentrations in plasma and urine (P<0.001), resulting in lower nadirs of the GFR (P<0.005). Correlations were found between both peak free platinum concentrations in plasma and urine and maxima of urinary albumin and N-acetyl-beta-D-glucosaminidase excretion. Within 12 months after completion of cisplatin therapy, children in the 1-h bolus group had recovered only partially from subclinical nephrotoxicity, with five out of six showing pathological proteinuria. The results provide clear evidence that long-term ciplatin infusions are less nephrotoxic than repetitive bolus infusions.

Adolescent↗
PubMed2001

[Practice and complications of spinal anesthesia in African tropical countries].

OBJECTIVE: To evaluate the risk of the practice of spinal anaesthesia (SA) in African tropics. STUDY DESIGN: Prospective study in multiple centres over a two years period. PERSONS: Twenty-one anaesthesiologists and anaesthetist nurses covering ten African countries. METHODS: Two anonymous questionnaires; the first, filled in each anaesthetic problem occurred, to define the type of incident or accident, and its circumstances; the second was designed to define the position occupied, to quantify the global anaesthetic activity, the number of SA, and to value the number of complications or deaths linked to SA. RESULTS: Six anaesthesiologists and one anaesthetist nurse replied to the study, covering six sites in five different countries (Senegal, Chad, Central African Republic, Niger and Madagascar). On the 18,432 anaesthetic acts collected, 2,703 (14.7%) were SA. In the well-equipped centres, general anaesthesia was predominant with a frequency of over 75%. However in the not so well equipped centres or those which supplies were more problematical, SA technique was used with a frequency varying from 48.9 to 68.7%. Forty incidents and accidents were reported (1.5%), five led to the death of the patient (0.2%). Among the seven cardiac arrests (0.3%), four were fatal (0.1%). Eight of the ten accidents and all of the deaths occurred in the least equipped centres. Eight of ten accidents happened during emergency caesarean sections. All cardiac arrests were preceded by a severe hypovolemia. For the four deaths after cardiac arrest, an anaesthetist nurse with isobaric bupivacaine 0.5% carried out SA. CONCLUSIONS: This study showed that the practice of SA in African tropics was performing in different practice conditions and people qualification than they were in France. The frequency of cardiac arrests and deaths was respectively five and 20 times more important, in those conditions. The first conclusion that can be drawn from this study is that it is questionable to use SA for emergency Caesarean section under hypovolemic condition. The second is the necessity for specific training on the local anaesthesia for anaesthetist nurses but also training to choose the anaesthesia best adapted to the surgery, the condition of the patient and the means available.

Adolescent↗
PubMed2001

The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community.

OBJECTIVES: To develop a simple method for identifying community-dwelling vulnerable older people, defined as persons age 65 and older at increased risk of death or functional decline. To assess whether self-reported diagnoses and conditions add predictive ability to a function-based survey. DESIGN: Analysis of longitudinal survey data. SETTING: A nationally representative community-based survey. PARTICIPANTS: Six thousand two hundred five Medicare beneficiaries age 65 and older. MEASUREMENTS: Bivariate and multivariate analyses of the Medicare Current Beneficiary Survey; development and comparison of scoring systems that use age, function, and self-reported diagnoses to predict future death and functional decline. RESULTS: A multivariate model using function, self-rated health, and age to predict death or functional decline was only slightly improved when self-reported diagnoses and conditions were included as predictors and was significantly better than a model using age plus self-reported diagnoses alone. These analyses provide the basis for a 13-item function-based scoring system that considers age, self-rated health, limitation in physical function, and functional disabilities. A score of >or=3 targeted 32% of this nationally representative sample as vulnerable. This targeted group had 4.2 times the risk of death or functional decline over a 2-year period compared with those with scores <3. The receiver operating characteristics curve had an area of.78. An alternative scoring system that included self-reported diagnoses did not substantially improve predictive ability when compared with a function-based scoring system. CONCLUSIONS: A function-based targeting system effectively and efficiently identifies older people at risk of functional decline and death. Self-reported diagnoses and conditions, when added to the system, do not enhance predictive ability. The function-based targeting system relies on self-report and is easily transported across care settings.

Activities of Daily Living↗
PubMed2001

Endocrinological study on growth retardation in Rett syndrome.

AIM: To determine whether primary or secondary growth hormone (GH) deficiency has a causative role in linear growth retardation, a key feature in Rett syndrome (RTT). METHODS: In 38 patients with Rett syndrome a variable set of investigations was performed including assays of growth and thyroid hormones, gonadotropins, gonadal and adrenal steroids and determination of bone age. Not all measurements were attainable from all patients. In three patients the 24-h growth hormone secretion profile was evaluated using the pulsar method. RESULTS: The bone age determined in 24 patients was found to be normal in 8, retarded in 9 and accelerated in 7 patients. Insulin-like growth factor (IGF)-1 was low in 8 out of 23 patients. IGF-binding protein (IGFBP)-3 and insulin and arginine-stimulated growth hormone secretion were both normal, indicating normal GH secretion in the majority of patients. The 24-h GH secretion profile in the first patient showed a normal day/night rhythm and a normal increase in nocturnal GH secretion. The second patient's overall GH secretion was normal but there was no day/night rhythm. The third patient showed borderline low GH secretion. Normal age-appropriate plasma values were found for the thyroid hormones (T4, TSH), TSH-night rhythm, oestradiol, prolactin and cortisol (08.00, 18.00). CONCLUSION: Our study provides no evidence that growth retardation in RTT is caused by growth hormone deficiency. A disturbed hypothalamic control cannot be excluded but it is unlikely that this is the major cause of growth retardation in RTT.

Adolescent↗
PubMed2001

Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats.

The cardiovascular system is currently considered a target for particulate matter, especially for ultrafine particles. In addition to autonomic or cytokine mediated effects, the direct interaction of inhaled materials with the target tissue must be examined to understand the underlying mechanisms. In the first approach, pulmonary and systemic distribution of inhaled ultrafine elemental silver (EAg) particles was investigated on the basis of morphology and inductively coupled plasma mass spectrometry (ICP-MS) analysis. Rats were exposed for 6 hr at a concentration of 133 microg EAg m(3) (3 x 10(6) cm(3), 15 nm modal diameter) and were sacrificed on days 0, 1, 4, and 7. ICP-MS analysis showed that 1.7 microg Ag was found in the lungs immediately after the end of exposure. Amounts of Ag in the lungs decreased rapidly with time, and by day 7 only 4% of the initial burden remained. In the blood, significant amounts of Ag were detected on day 0 and thereafter decreased rapidly. In the liver, kidney, spleen, brain, and heart, low concentrations of Ag were observed. Nasal cavities, especially the posterior portion, and lung-associated lymph nodes showed relatively high concentrations of Ag. For comparison, rats received by intratracheal instillation either 150 microL aqueous solution of 7 microg silver nitrate (AgNO(3) (4.4 microg Ag) or 150 microL aqueous suspension of 50 microg agglomerated ultrafine EAg particles. A portion of the agglomerates remained undissolved in the alveolar macrophages and in the septum for at least 7 days. In contrast, rapid clearance of instilled water-soluble AgNO(3) from the lung was observed. These findings show that although instilled agglomerates of ultrafine EAg particles were retained in the lung, Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well as after instillation of AgNO(3), and entered systemic pathways.

Administration, Inhalation↗
PubMed2001

Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages.

Agglomerates of ultrafine particles (AUFPs) may cause adverse health effects because of their large surface area. To evaluate physiologic responses of immune cells, we studied whether agglomerates of 77-nm elemental carbon [(EC); specific surface area 750 m2/g] and 21 nm titanium dioxide (TiO(2) particles (specific surface area 50 m(2)/g) affect the release of lipid mediators by alveolar macrophages (AMs). After 60-min incubation with 1 microg/mL AUFP-EC (corresponding to 7.5 cm(2) particle surface area), canine AMs (1 x 10(6) cells/mL) released arachidonic acid (AA) and the cyclooxygenase (COX) products prostaglandin E(2) (PGE(2), thromboxane B(2), and 12-hydroxyheptadecatrienoic acid but not 5-lipoxygenase (5-LO) products. AUFP-TiO(2) with a 10-fold higher mass (10 microg/mL) than AUFP-EC, but a similar particle surface area (5 cm(2) also induced AMs to release AA and COX products. Agglomerates of 250 nm TiO(2) particles (specific surface area 6.5 m(2)/g) at 100 microg/mL mass concentration (particle surface area 6.5 cm(2) showed the same response. Interestingly, 75 cm(2)/mL surface area of AUFP-EC and 16 cm(2)/mL surface area of AUFP-TiO(2) additionally induced the release of the 5-LO products leukotriene B(4) and 5-hydroxyeicosatetraenoic acid. Respiratory burst activity of stimulated canine neutrophils was partially suppressed by supernatants of AMs treated with various mass concentrations of the three types of particles. Inhibition of neutrophil activity was abolished by supernatants of AMs treated with COX inhibitors prior to AUFP-incubation. This indicates that anti-inflammatory properties of PGE(2) dominate the overall response of lipid mediators released by AUFP-affected AMs. In conclusion, our data indicate that surface area rather than mass concentration determines the effect of AUFPs, and that activation of phospholipase A(subscript)2(/subscript) and COX pathway occurs at a lower particle surface area than that of 5-LO-pathway. We hypothesize a protective role of PGE(2) in downregulating potential inflammatory reactions induced by ultrafine particles.

Air Pollutants↗
PubMed2001

Autoregulation of the gonadotropin-releasing hormone (GnRH) system during puberty: effects of antagonistic versus agonistic GnRH analogs in a female rat model.

To address whether gonadotropin-releasing hormone (GnRH) regulates its own expression and the expression of its receptor in the hypothalamus and ovary, we treated five groups of prepubertal/peripubertal female rats from postnatal days 25-36 with either the GnRH agonist triptorelin (TRIP) or the GnRH antagonist cetrorelix (CET), each 10 or 100 microgram/day, or a placebo. We compared their effects regarding pubertal development, serum gonadotropins and the expression of GnRH and GnRH-receptor in the hypothalamus, pituitary, ovary and uterus. Onset of puberty was determined by vaginal opening, and expression levels of GnRH and GnRH-receptor were determined using either quantitative real-time PCR or competitive RT-PCR. Onset of puberty was retarded by both analogs but CET (100 microgram/day) inhibited while TRIP (10 and 100 microgram/day) stimulated serum gonadotropins (P<0.05). The expression of GnRH in the preoptic area did not show significant differences among the treatment groups but ovarian GnRH mRNA levels were significantly stimulated by CET (100 microgram/day). GnRH mRNA could not be detected in the uterus by either real-time PCR or competetive RT-PCR. The GnRH-receptor expression in the hypothalamus (preoptic area and mediobasal hypothalamus) did not vary among any of the groups, whereas in the pituitary GnRH-receptor mRNA levels were stimulated by TRIP (10 microgram/day) but inhibited by CET (100 microgram/day). In contrast, in the ovary GnRH-receptor mRNA levels were inhibited by both TRIP (100 microgram/day) and CET (100 microgram/day). Interestingly, the GnRH-receptor was even expressed in the uterus where it was strongly stimulated by both CET and TRIP in a dose-related manner. This shows that in addition to their different pituitary effects, the GnRH analogs cetrorelix and triptorelin exert different actions at the hypothalamic, ovarian and uterine level. This study also demonstrates an organ-specific regulation of GnRH and GnRH-receptor gene expression which is likely part of a local autoregulatory system. We conclude that the ovarian and uterine effects of GnRH analogs must be considered in addition to their known pituitary effects when deciding which GnRH analog is most suitable for treating precocious puberty.

Analysis of Variance↗