Search PubMed⌕ Search

Biomedical subjects

P Ammann

Publications and source records attributed to P Ammann.

At least 37 records · Page 2Linked to original sources
PubMed2001

Protein intake and bone growth.

Among osteotrophic nutrients, proteins play an important role in bone development, thereby influencing peak bone mass. Consequently, protein malnutrition during development can increase the risk of osteoporosis and of fragility fracture later in life. Both animal and human studies indicate that low protein intake can be detrimental for both the acquisition of bone mass during growth and its conservation during adulthood. Low protein intake impairs both the production and action of IGF-I (Insulin-like growth factor-I). IGF-I is an essential factor for bone longitudinal growth, as it stimulates proliferation and differentiation of chondrocytes in the epiphyseal plate, and also for bone formation. It can be considered as a key factor in the adjustments of calcium-phosphate metabolism required for normal skeletal development and bone mineralization during growth. In healthy children and adolescents, a positive association between the amount of ingested proteins and bone mass gain was observed in both sexes at the level of the lumbar spine, the proximal femur and the midfemoral shaft. This association appears to be particularly significant in prepubertal children. This suggests that, like for the bone response to either the intake of calcium or weight-bearing exercise, the skeleton would be particularly responsive to the protein intake during the years preceding the onset of pubertal maturation.

Animals↗
PubMed2000

Dietary protein restriction lowers plasma insulin-like growth factor I (IGF-I), impairs cortical bone formation, and induces osteoblastic resistance to IGF-I in adult female rats.

Dietary protein deficiency, common in elderly, is associated with decreased areal bone mineral density and plasma insulin-like growth factor I (IGF-I). To investigate the early adaptation of bone cells to protein restriction, 6-month-old female rats were pair-fed with isocaloric 15% (control) or 2.5% casein diets for 14 days. Animals were then treated daily with rhIGF-I/IGFBP-3 (1:4, 2.5 mg IGF-I/kg BW) or with vehicle for 10 days. After double-labeling, proximal metaphysis and mid-diaphysis of the tibia were analyzed histomorphometrically. Plasma osteocalcin, IGF-I, and urinary deoxypyridinoline were quantified. After 14 days of protein restriction, significant drops in plasma osteocalcin (13%) and IGF-I (37%), in periosteal formation (83%) and mineral apposition (49%) rates are observed, indicating a decreased osteoblast recruitment and activity. In cancellous bone, a significant decrease in active eroded surfaces (27%) and osteoclast number (24%) indicates a transient depression of resorption. In rats fed the 15% casein diet, rhIGF-I/IGFBP-3 increases cancellous (42%) and periosteal (600%) formation rates, indicating an increased osteoblast recruitment. In protein-restricted rats, rhIGF-I/IGFBP-3 fails to increase cancellous or periosteal bone formation and plasma osteocalcin is significantly lower than in 15% casein+rhIGF-I/ IGFBP-3 rats. Protein restriction induces osteoblast resistance to rhIGF-I/IGFBP-3 in both bone envelopes. Low plasma IGF-I and osteoblast resistance to IGF-I, may contribute to the impaired periosteal formation.

Animals↗
PubMed2000

Protein undernutrition-induced bone loss is associated with decreased IGF-I levels and estrogen deficiency.

Protein undernutrition is a known factor in the pathogenesis of osteoporotic fracture in the elderly, but the mechanisms of bone loss resulting from this deficiency are still poorly understood. We investigated the effects of four isocaloric diets with varying levels of protein content (15, 7.5, 5, and 2.5% casein) on areal bone mineral density (BMD), bone ultimate strength, histomorphometry, biochemical markers of bone remodeling, plasma IGF-I, and sex hormone status in adult female rats. After 16 weeks on a 2.5% casein diet, BMD was significantly decreased at skeletal sites containing trabecular or cortical bone. Plasma IGF-I was decreased by 29-34% and no estrus sign in vaginal smear was observed. To investigate the roles of estrogen deficiency and protein undernutrition, the same protocol was used in ovariectomized (OVX) or sham-operated (SHAM) rats, pair-fed isocaloric diets containing either 15 or 2.5% casein. Trabecular BMD was decreased by either manipulation, with effects appearing to be additive. Cortical BMD was decreased only in rats on a low-protein diet. This was accompanied by an increased urinary deoxypyridinoline excretion without any change in osteocalcin levels, suggesting an uncoupling between resorption and formation. Isocaloric protein undernutrition decreased bone mineral mass and strength. This effect might be related to decreased plasma IGF-I and/or estrogen deficiency with a consequent imbalance in bone remodeling.

Animals↗
PubMed2000

Dietary protein deficiency induces osteoporosis in aged male rats.

Low dietary intake is common in elderly males with low femoral neck areal bone mineral density (BMD). To evaluate the selective influence of a low-protein diet in the pathogenesis of osteoporosis in males and to uncover early and late adaptation of bone cells to protein deficiency, 8-month-old male rats were pair-fed a control (15% casein) or isocaloric low-protein (2.5% casein) diet for 1 or 7 months. BMD, bone ultimate strength, stiffness, and absorbed energy were measured in tibia proximal metaphysis and diaphysis. After double-labeling, histomorphometric analysis was performed at the same sites. Serum osteocalcin, insulin-like growth factor I (IGF-I), and urinary deoxypyridinoline excretion were measured. In proximal tibia, isocaloric low-protein diet significantly decreases BMD (12%), cancellous bone mass (71%), and trabecular thickness (Tb.Th; 30%), resulting in a significant reduction in ultimate strength (27%). In cortical middiaphysis, a low-protein diet decreases BMD (9%) and enlarges the medullary cavity (36%), leading to cortical thinning and lower mechanical strength (20%). In cancellous bone, protein deficiency transiently depresses the bone formation rate (BFR; 60%), osteoid seam thickness (15%), and mineral apposition rate (MAR; 20%), indicating a decrease in osteoblast recruitment and activity. Cortical loss (15%) results from an imbalance between endosteal modeling drifts with impaired BFR (70%). From the first week of protein deficiency, osteocalcin and IGF-I levels drop significantly. Bone resorption activity and urinary deoxypyridinoline remain unchanged throughout the experiment. Protein deficiency in aged male rats induces cortical and trabecular thinning, and decreases bone strength, in association with a remodeling imbalance with a bone formation impairment and a decrease in IGF-I levels.

Aging↗
PubMed2000

Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries.

STUDY OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINC) is a life-threatening event with many open questions for physicians and patients. There are little data concerning the prognosis for patients with MINC. DESIGN: Retrospective follow-up study. SETTING: Tertiary referral center. PATIENTS: Patients with MINC were investigated and compared to age- and sex-matched control subjects with myocardial infarction due to coronary artery disease (CAD). The patients were examined clinically using stress exercise and hyperventilation tests. Migraine and Raynaud's symptoms were determined by means of a standardized questionnaire. Serum lipoproteins; the seroprevalence of cytomegalovirus, Helicobacter pylori, and Chlamydia pneumoniae infections; and the most frequent causes of thrombophilia were assessed. MEASUREMENTS AND RESULTS: From > 4,300 angiographies that were performed between 1989 and 1996, 21 patients with MINC were identified. The mean +/- SD patient age at the time of myocardial infarction was 42 +/- 7.5 years. When compared to control subjects (n = 21), patients with MINC had fewer risk factors for CAD. In contrast, MINC patients had more frequent febrile reactions prior to myocardial infarction (six patients vs zero patients; p < 0.05), and the migraine score was significantly higher (7.1 +/- 6.3 vs 2.2 +/- 4.1; p < 0.01). The seroprevalence of antibodies against cytomegalovirus, C pneumoniae, and H pylori tended to be higher in patients with MINC and CAD as compared to matched healthy control subjects. Three patients with MINC vs none with CAD had coagulopathy. During follow-up (53 +/- 37 months), no major cardiac event occurred in the MINC group; no patients with MINC vs nine with CAD (p = 0.0001) underwent repeated angiography. CONCLUSION: High migraine score and prior febrile infection together with a lower cardiovascular risk profile are compatible with an inflammatory and a vasomotor component in the pathophysiology of the acute coronary event in MINC patients. The prognosis for these patients is excellent.

Adult↗
PubMed2000

Essential amino acid supplements increase muscle weight, bone mass and bone strength in adult osteoporotic rats.

Protein undernutrition is known to play an important role in the pathogenesis of osteoporotic fracture in elderly. The mechanisms underlying the bone loss in protein undernutrition appeared to be related to an uncoupling between increased bone resorption and bone formation. This was associated with decreased plasma IGF-I levels, with anoestrus and decreased muscle mass. Reversibility of protein undernutrition-induced bone loss was investigated in ovariectomized adult rats, which were fed isocaloric 2.5 % casein diet (OVX2.5) for 16 weeks. Then, the animals were given a supplement of essential amino-acids in similar proportion to that of casein at doses of 2.5% (EAA2.5) or 5% (EAA5) of total food intake for an additional 16 weeks. Essential amino acid supplements increased bone mineral mass and strength in ovariectomized protein-deprived rats. EAA supplements were associated with stimulated bone formation and reduced bone resorption, with increment of plasma IGF-I and of limb muscle mass weight. These results suggest that nutritional intervention with essential amino acid supplements can increase bone mineral mass, bone strength and muscle mass in osteoporotic rats possibly by correcting IGFI status.

Journal Article↗
PubMed1999

[Drug addict with ptosis. Myasthenia gravis].

We report a 29 year old female drug addict seen in the emergency room with neck abscesses, dysphagia and a symmetric ptosis. Initially misinterpreted as adverse effect of illegal drug intake these symptoms were due to myasthenia gravis. This case shows an important differential diagnosis of ptosis common in drug addicts.

Adult↗
PubMed1999

Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines.

Osteoporosis, which is defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk, is a major health issue worldwide. Among the various strategies to prevent and cure this devastating ailment, an important objective is the development of new efficacious and safe drugs. This situation prompted the World Health Organization (WHO) to provide a comprehensive statement of guiding principles for the design, implementation and interpretation of both preclinical testing and clinical trials in osteoporosis. These guidelines, which are now available, underline the crucial importance of the preclinical evaluation, particularly for assessing the effect of an intervention on bone strength. This concept is heightened by the lack of a validated technique for noninvasively evaluating bone strength in humans and the multiple difficulties and heavy burden inherent in the evaluation of fracture rate in clinical trials. The WHO guidelines emphasize that a comprehensive and adequate preclinical program is expected to provide key information on the relationship between bone mass and strength and thus attenuate the burden of clinical studies. The present report provides a review of experimental evidence in support of the preclinical program as proposed in the WHO guidelines. This program is based on the recent development and refinement of animal models of osteoporosis that mimic the human condition according to the conceptual definition of the disease. Many preclinical studies carried out in appropriate animal models with agents that exert either antiresorbing or anabolic effects on bone indicate that they have been highly predictive of the drug action in humans in terms of both bone mass and remodeling, as well as of bone strength whenever fracture rate has been documented in clinical trials. Based on this evidence the WHO guidelines propose strategies according to which the results of preclinical evaluation will determine the end-points required in the different phases of the clinical development of the drug. Such a distribution of task assignment between preclinical and clinical programs should optimize the progress of research available to patients already suffering from or at risk of osteoporosis.

Animals↗
PubMed1999

The new selective estrogen receptor modulator MDL 103,323 increases bone mineral density and bone strength in adult ovariectomized rats.

Selective estrogen receptor modulators (SERMs) can prevent the bone loss induced by ovariectomy (OVX), but it is not established whether they can increase bone mass and strength in a curative protocol in ovariectomized osteopenic animals. We investigated the influence of a SERM of the new generation, MDL 103,323, on areal bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry, bone strength and remodeling in OVX osteopenic rats. Nine weeks after OVX, 8-month-old rats were divided into six groups of 10 animals. MDL 103,323 was given by gavage at doses of 0.01, 0.1 or 0.6 mg/kg body weight, 5 days a week. The effect of MDL 103,323 was compared with that of the bisphosphonate pamidronate (APD), which was injected subcutaneously at a dose of 1.6 mmol/kg body weight for 5 days every 4 weeks. Lumbar spine (LS), femoral neck (FN), proximal tibia (PT) and midshaft tibia (MT) BMD, bone strength, and proximal tibia histomorphometry, serum osteocalcin, urinary total deoxypyridinoline and serum insulin-like growth factor I (IGF-I) were measured. After 16 weeks of treatment, BMD changes (means +/- SEM) were -11.4 +/- 2. 2, +4.0 +/- 2.1 and +6.4 +/- 1.0% respectively in OVX controls, in rats treated with 0.1 mg/kg MDL 103,323 (p<0.05) and in APD-treated rats (p<0.02) at the level of LS; -0.4 +/- 1.1, +6.7 +/- 1.4, +7.2 +/- 1.8% (p<0.01 and NS) at the level of FN; and -2.6 +/- 1.2%, +5.8 +/- 1.2, +6.9 +/- 1.4% (p<0.03 and 0.01) at the level of PT. MDL 103, 323-treated animals had a higher trabecular bone volume, a higher number of trabeculae and smaller intertrabecular spaces compared with OVX controls. Vertebral body ultimate strength was 186 +/- 13, 292 +/- 16, 249 +/- 23 N (p<0.05) in OVX controls, MDL 103, 323-treated rats and APD-treated rats, respectively. The administration of 0.6 mg/kg of MDL 103,323 did not further increase BMD or bone strength, indicating a bell-shaped dose-response curve. MDL 103,323 lowered plasma osteocalcin concentration and urinary deoxypyridinoline excretion. In rats treated with 0.1 mg/kg MDL 103, 323, plasma IGF-I was increased as compared with OVX controls (664 +/- 36 ng/ml vs 527 +/- 39 ng/ml, p<0.05). In conclusion, these results indicate that this new SERM positively influences BMD and lumbar spine bone strength in estrogen-deficient rats.

Analysis of Variance↗
PubMed1999

Comparison of the effect of medium-chain and long-chain triacylglycerols on calcium absorption in healthy subjects.

BACKGROUND: The absorption efficiency of calcium in humans is low. Some studies in infants have shown that calcium absorption can be increased by adding medium-chain triacylglycerols to the formula diet. OBJECTIVE: The effect of medium- and long-chain triacylglycerols on calcium absorption was studied in 18 healthy, young men. The results were compared with data obtained from calcium ingestion of a protein-carbohydrate formula devoid of triacylglycerols. DESIGN: Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by using a deconvolution method. RESULTS: The total fractional calcium absorption measured in the presence of medium-chain triacylglycerols (0.236 +/- 0.016) or from a protein-carbohydrate formula without triacylglycerols (0.235 +/- 0.012) was not significantly different. The same result was observed with long-chain triacylglycerols (0.309 +/- 0.026) and the protein-carbohydrate formula (0.275 +/- 0.012). No kinetic parameters were significantly different regardless of the diet (protein-carbohydrate, medium-chain triacylglycerol, or long-chain triacylglycerol). This suggests that the same mechanism for calcium absorption was operative. CONCLUSIONS: Triacylglycerols had no direct effect on calcium absorption from a protein-carbohydrate formula in healthy subjects. These data do not support the use of medium-chain triacylglycerols as adjuvants to increase the absorption of calcium in healthy adults.

Adult↗
PubMed1999

Osteoblasts are a new target for prolactin: analysis of bone formation in prolactin receptor knockout mice.

Bone development is a multistep process that includes patterning of skeletal elements, commitment of hematopoietic and/or mesenchymental cells to chondrogenic and osteogenic lineages, and further differentiation into three specialized cell types: chondrocytes in cartilage and osteoblasts and osteoclasts in bone. Although PRL has a multitude of biological actions in addition to its role in the mammary gland, very little is known about its effect on bone. Mice carrying a germline null mutation for the PRL receptor gene have been produced in our laboratory and used to study the role of PRL in bone formation. In -/- embryos, we observed an alteration in bone development of calvaria. In adults, histomorphometric analysis showed that the absence of PRL receptors leads to a decrease in bone formation rate using double calcein labeling and a reduction of bone mineral density, measured by dual energy x-ray absorptiometry. In addition, serum estradiol, progesterone, testosterone, and PTH levels were analyzed. We also established that osteoblasts, but not osteoclasts, express PRL receptors. This suggests that an effect of PRL on osteoblasts could be required for normal bone formation and maintenance of bone mass. Thus, the PRL receptor knockout mouse model provides a new tool to investigate the involvement of PRL in bone metabolism.

Absorptiometry, Photon↗
PubMed1999

Relapsing Whipple's disease presenting with hypopituitarism.

A 44-year-old man with a history of Whipple's disease 8 years ago presented with recurrent grand mal seizures and signs of hypopituitarism on physical examination. Magnetic resonance imaging of the brain revealed a hypothalamic lesion of 1 cm diameter in the region of the rostral infundibulum. Hypopituitarism was confirmed by low levels of serum cortisol, free testosterone and free thyroxine without an elevated TSH. Whipple encephalitis with hypothalamic involvement was suggested and verified by positive polymerase chain reaction (PCR) for Tropheryma whippelii in the cerebrospinal fluid. PCR for T. whippelii has become an important diagnostic tool for establishing the diagnosis of Whipple's disease especially in patients with unusual presentations and if the diagnosis cannot be confirmed histologically. Whipple's disease should be included in the differential diagnosis in hypopituitarism caused by infectious disease.

Actinobacteria↗
PubMed1998

Chloroform-induced cytolethality in freshly isolated male B6C3F1 mouse and F-344 rat hepatocytes.

Chloroform is carcinogenic in rodents but is not mutagenic or DNA reactive. Chloroform-induced hepatocarcinogenesis in rodents is believed to be secondary to events associated with cytotoxicity and cell proliferation. Understanding the mechanisms of chloroform toxicity may provide insights into the mechanisms of carcinogenicity. The goal of these studies was to characterize the cytotoxicity of chloroform in male B6C3F1 mouse and F-344 rat hepatocytes in vitro. We used an in vitro suspension-culture system that reproduced the exposure of the liver to chloroform and the expression of toxicity in vivo. Simulations of a physiologically based dosimetry model for chloroform indicated that the livers of mice and rats were exposed to chloroform concentrations up to 5 mM for 3 h after hepatotoxic doses of chloroform. Freshly isolated male mouse and rat hepatocytes were exposed to chloroform in sealed flasks and then cultured for 24 h as monolayers. Following a 2- or 3-h exposure in suspension, chloroform induced concentration-dependent cytotoxicity (lactate dehydrogenase release) in culture at concentrations higher than 1 mM. Cytolethality was not increased under reduced oxygen tension, indicating that reductive metabolism does not contribute to chloroform-induced toxicity. A threshold of 1 mM chloroform was also found for glutathione (GSH) depletion, with a 50% depletion at 3.8 mM after 2 h. Addition of dithiothreitol, a reducing agent, did not prevent chloroform-induced toxicity, indicating that oxidation of sulfhydryl groups is not critical for toxicity. The lack of protein sulfhydryl group depletion is consistent with this conclusion. Cotreatment with the cytochrome P450 inhibitor 1-phenylimidazole prevented both cytolethality and GSH depletion, indicating that metabolism is necessary for chloroform-induced toxicity. Both species exhibited similar sensitivity toward chloroform toxicity, indicating that toxicity is not sufficient to explain different susceptibility in heptocarcinogenicity. As chloroform metabolism is saturated in the micromolar range, our results indicate that both metabolism and exposure of the liver cells to high concentrations of chloroform are required for toxicity.

Animals↗
PubMed1998

[Cor triatriatum dexter of an adult].

Cor triatriatum dexter is a rare congenital malformation in which a membrane divides the right atrium into two chambers. The membrane represents a persistence of the right sinus venosus valve (RSV). Normally the RSV regresses between the 9th and 15th week of gestation, as the cephalic portion forms the crista terminalis and the caudal portion develops into the Eustachian and Thebesian valve. Any failure in the regression process may result in remnants of RSV as a simple muscle bar, a Chiari-network or a fenestrated or unfenestrated membrane (cor triatriatum dexter). We describe a patient with cor triatriatum dexter in whom diagnosis was made several years after successful valvulotomy procedure for severe congenital valvular pulmonary stenosis.

Adult↗