HEPATOLOGY, Issue 1 2008
Steven M. Kawut
Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes · second · cm,5, and pulmonary capillary wedge pressure , 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio = 2.90, 95% confidence interval 1.20-7.01, P = 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio = 4.02, 95% confidence interval 1.14-14.23, P = 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio = 0.24, 95% confidence interval 0.09-0.65, P = 0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension. Conclusion: Female sex and autoimmune hepatitis were associated with an increased risk of portopulmonary hypertension, whereas hepatitis C infection was associated with a decreased risk in patients with advanced liver disease. Hormonal and immunologic factors may therefore be integral to the development of portopulmonary hypertension. (HEPATOLOGY 2008.) [source]

Hormonal and Biochemical Parameters and Osteoporotic Fractures in Elderly Men

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2000
Dr. Jacqueline R. Center
Abstract Low testosterone has been associated with hip fracture in men in some studies. However, data on other hormonal parameters and fracture outcome in men is minimal. This study examined the association between free testosterone (free T) estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps strength, femoral neck bone mineral density (FN BMD), and fracture data (1989,1997) also were obtained. Fractures were classified as major (hip, pelvis, proximal tibia, multiple rib, vertebral, and proximal humerus) or minor (remaining distal upper and lower limb fractures). Fifty-four subjects had a fracture (24 major and 30 minor). There was no association between minor fractures and any hormonal parameter. Risk of major fracture was increased 2-fold for each SD increase in age, decrease in weight and height, and increase in SHBG, and risk of major fracture was increased 3-fold for each SD decrease in quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression). Independent predictors of major fracture were FN BMD, 2.7 (1.5,4.7; odds ratio [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5,5.3); and SHBG, 1.7 (1.2,2.4). An abnormal value for three factors resulted in a 30-fold increase in risk but only affected 2% of the population. It is not immediately apparent how 25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk. They may be markers for biological age or health status not measured by methods that are more traditional and as such may be useful in identifying those at high risk of fracture. [source]

Women's Decision Making About the Use of Hormonal and Nonhormonal Remedies for the Menopausal Transition

JOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 6 2003
Rosemary Theroux
Objective: To critically review qualitative research on women's decision making about the use of hormonal and nonhormonal remedies for the menopausal transition. Data Sources: Computerized searches in CINAHL, MEDLINE, Medscape, and PsychINFO databases, using the keywords decision making, hormone therapy, herbal remedies, attitude toward hormone therapy, and qualitative research; and ancestral bibliographies. Study Selection: Articles from indexed journals from 1982 to 2001 in the English language relevant to the keywords were evaluated. Sixteen studies met inclusion criteria and were included in the analysis. Data Extraction: Study findings were organized into several categories and compared and contrasted across publications and categories. Data Synthesis: Half of the researchers described decision making as a weighing of benefits and risks. Women's considerations, beliefs, and values, as well as interaction with the environment, were primary influences on the process. Conclusions: Major gaps in care for midlife women were identified. Women need information about the process of menopause and the range of available options for menopause management. Nurses can play a major role in providing information, counseling, and developing decision aids. Women's values and beliefs, cultures, life contexts, and desire for involvement in the decision should guide interventions. [source]

Hormonal and nutritional regulation of insect fat body development and function

ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2009
Ying Liu
Abstract The insect fat body is an organ analogue to vertebrate adipose tissue and liver and functions as a major organ for nutrient storage and energy metabolism. Similar to other larval organs, fat body undergoes a developmental "remodeling" process during the period of insect metamorphosis, with the massive destruction of obsolete larval tissues by programmed cell death and the simultaneous growth and differentiation of adult tissues from small clusters of progenitor cells. Genetic ablation of Drosophila fat body cells during larval-pupal transition results in lethality at the late pupal stage and changes sizes of other larval organs indicating that fat body is the center for pupal development and adult formation. Fat body development and function are largely regulated by several hormonal (i.e. insulin and ecdysteroids) and nutritional signals, including oncogenes and tumor suppressors in these pathways. Combining silkworm physiology with fruitfly genetics might provide a valuable system to understand the mystery of hormonal regulation of insect fat body development and function. © 2009 Wiley Periodicals, Inc. [source]

Hormonal and metabolic effects of morning or evening dosing of the dipeptidyl peptidase IV inhibitor vildagliptin in patients with type 2 diabetes

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010
Yan-Ling He
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Vildagliptin is an orally active, potent inhibitor of dipeptidyl peptidase IV and was developed for the treatment of type 2 diabetes. , In clinical trials, once or twice daily dosing with vildagliptin (up to 100 mg day,1) has been shown to reduce endogenous glucose production and fasting plasma glucose in patients with type 2 diabetes. , The comparative efficacy of vildagliptin under a morning vs. evening dosing regimen has not previously been determined. WHAT THIS STUDY ADDS , Once daily dosing with vildagliptin 100 mg for 28 days improved glycaemic control in patients with type 2 diabetes independent of whether vildagliptin was administered in the morning or evening. , Morning or evening dosing with vildagliptin had similar effects on 24 h glycaemic control and plasma concentrations of the hormones insulin, glucagon and glucagon-like peptide 1. AIM This randomized, double-blind, crossover study compared post-prandial hormonal and metabolic effects of vildagliptin, (an oral, potent, selective inhibitor of dipeptidyl peptidase IV [DPP-4]) administered morning or evening in patients with type 2 diabetes. METHODS Forty-eight patients were randomized to once daily vildagliptin 100 mg administered before breakfast or before dinner for 28 days then crossed over to the other dosing regimen. Blood was sampled frequently after each dose at baseline (day ,1) and on days 28 and 56 to assess pharmacodynamic parameters. RESULTS Vildagliptin inhibited DPP-4 activity (>80% for 15.5 h post-dose), and increased active glucagon-like peptide-1 compared with placebo. Both regimens reduced total glucose exposure compared with placebo (area under the 0,24 h effect,time curve [AUE(0,24 h)]: morning ,467 mg dl,1 h, P= 0.014; evening ,574 mg dl,1 h, P= 0.003) with no difference between regimens (P= 0.430). Reductions in daytime glucose exposure (AUE(0,10.5 h)) were similar between regimens. Reduction in night-time exposure (AUE(10.5,24 h) was greater with evening than morning dosing (,336 vs.,218 mg dl,1 h, P= 0.192). Only evening dosing significantly reduced fasting plasma glucose (,13 mg dl,1, P= 0.032) compared with placebo. Insulin exposure was greater with evening dosing (evening 407 µU ml,1 h; morning 354 µU ml,1 h, P= 0.050). CONCLUSIONS Both morning and evening dosing of once daily vildagliptin 100 mg significantly reduced post-prandial glucose in patients with type 2 diabetes; only evening dosing significantly decreased fasting plasma glucose. Although evening dosing with vildagliptin 100 mg tended to decrease night-time glucose exposure more than morning dosing, both regimens were equally effective in reducing 24 h mean glucose exposure (AUE(0,24 h)) in patients with type 2 diabetes. [source]

Pubertal Development: Correspondence Between Hormonal and Physical Development

CHILD DEVELOPMENT, Issue 2 2009
Elizabeth A. Shirtcliff
Puberty is advanced by sex hormones, yet it is not clear how it is best measured. The interrelation of multiple indices of puberty was examined, including the Pubertal Development Scale (PDS), a picture-based interview about puberty (PBIP), and a physical exam. These physical pubertal measures were then associated with basal hormones responsible for advancing puberty. Participants included 160 early adolescents (82 boys). Puberty indices were highly correlated with each other. The physical exam stages correlated well with boys' and girls' testosterone and dehydroepiandrosterone and less so with girls' estradiol. The PDS and PBIP were similarly related to basal hormones. Self-report may be adequate when precise agreement is unnecessary. Multiple measures of puberty are viable options, each with respective strengths. [source]

Long-term (up to 18 years) effects on GH/IGF-1 hypersecretion and tumour size of primary somatostatin analogue (SSTa) therapy in patients with GH-secreting pituitary adenoma responsive to SSTa

CLINICAL ENDOCRINOLOGY, Issue 2 2007
Jean Christophe Maiza
Summary Context The role of somatostatin analogues (SSTa) in the treatment of acromegaly. Objective To evaluate the antihormonal and antitumour efficacy of long-term (up to 18 years) primary treatment with SSTa in patients with GH-secreting pituitary adenoma responsive to SSTa. Design An open, prospective, single-centre, clinical study. Patients Thirty-six acromegalic patients, aged 17,75 years (postoral glucose tolerance test GH > 1 µg/l, increased IGF-1 for age and sex), were monitored in a single centre and treated with SSTa as first-line therapy. The mean pretreatment GH level was 13·5 ± 3·1 µg/l, and IGF-1 (as a percentage of the value over the normal range) was 302 ± 26%. The patients had macroadenoma (n = 25), microadenoma (n = 8) or empty sella turcica (n = 3). The mean duration of treatment was 8 years (range 3,18 years). Hormonal and morphological monitoring was undertaken after 6 months, and then the patients were followed annually. Results After 1 year, the mean GH and IGF-1 levels had reduced considerably (GH: 2·4 ± 0·3 µg/l; IGF-1; 174 ± 14%, P < 0·01), and they continued to decrease over 10 years, with a mean GH level of 1·6 ± 0·1 µg/l and IGF-1 of 123 ± 18% (P = 0·02). GH < 2 µg/l, normal IGF-1, or both were observed in 25 (70%), 24 (67%) and 21 (58%) patients, respectively. The mean reduction in tumour volume was 43% (range 13,97%) and shrinkage > 20% was obtained in 21 patients (72%). SSTa treatment was well tolerated with few digestive or metabolic side-effects. Conclusion Long-term (up to 18 years) treatment with SSTa used as first-line therapy is effective from both an antihormonal and antitumour perspective, and is well tolerated in acromegalic patients. [source]

Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs

ACTA PHYSIOLOGICA, Issue 4 2004
R. C. E. Francis
Abstract Aim:, This study investigates angiotensin II and endothelin-1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. Methods:, Conscious dogs were pre-treated with angiotensin II type 1 (AT1) and/or endothelin-A (ETA) receptor blockers or not. Protocol 1: After a 60-min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT-627. Protocol 4: Likewise, but with combined AT1plus ETAblockade. Results:, In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1-fold), endothelin-1 (1.13-fold), vasopressin (116-fold), and adrenaline concentrations (3.2-fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (,40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. Conclusions:, Angiotensin II is more important than endothelin-1 for the short-term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin-1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin-1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage-induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output , but not MAP , was similar in all protocols. [source]

Fate of fatty acids at rest and during exercise: regulatory mechanisms

ACTA PHYSIOLOGICA, Issue 4 2003
M. D. Jensen
Abstract Fatty acids are a major fuel source for humans both at rest and during exercise. Plasma free fatty acids (FFA), although present only in micromolar concentrations, are the major circulating lipid fuel. FFA availability can increase two- to four-fold with moderate intensity exercise. Other potential sources of fatty acids include circulating very low-density lipoprotein (VLDL) triglycerides (TGs) (,1/5 the fuel availability of FFA) and intramyocellular TGs (,2 mmol kg,1 muscle). At rest ,40% of systemic FFA uptake occurs in the splanchnic bed and uptake in legs is ,15,20%. During leg exercise the uptake of FFA in leg tissue increases to 30,60% of systemic uptake and splanchnic uptake decreases to 15%. The fate of VLDL TG fatty acids has not been adequately studied. Intramyocellular TG hydrolysis increases during exercise, but the factors that regulate this response are not clear. The fact that contraction of isolated muscles can stimulate the hydrolysis and oxidation of intramyocellular TGs (in the absence of hormonal or neural input) suggests an intracellular regulation of this process. Additional regulation from changes in catecholamines and insulin may also occur. During moderate intensity exercise circulating FFA and intramyocellular TG provide roughly equal portions of fatty acids for oxidation. In addition to endurance training, dietary factors have been shown to modulate the fatty acid oxidation response to exercise. Much remains to be learned about fatty acid trafficking during exercise. What role do VLDL TG play? How is the oxidation of intramyocellular TGs regulated? Techniques to address these questions in humans are only now becoming available. [source]

The cognitive phenotype in Klinefelter syndrome: A review of the literature including genetic and hormonal factors

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2009
Richard Boada
Abstract Klinefelter syndrome (KS) or 47,XXY occurs in ,1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:284,294. [source]

Neurophysiology of hunger and satiety

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2008
Pauline M. Smith
Abstract Hunger is defined as a strong desire or need for food while satiety is the condition of being full or gratified. The maintenance of energy homeostasis requires a balance between energy intake and energy expenditure. The regulation of food intake is a complex behavior. It requires discrete nuclei within the central nervous system (CNS) to detect signals from the periphery regarding metabolic status, process and integrate this information in a coordinated manner and to provide appropriate responses to ensure that the individual does not enter a state of positive or negative energy balance. This review of hunger and satiety will examine the CNS circuitries involved in the control of energy homeostasis as well as signals from the periphery, both hormonal and neural, that convey pertinent information regarding short-term and long-term energy status of the individual. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:96,104. [source]

Remodeling of an identified motoneuron during metamorphosis: central and peripheral actions of ecdysteroids during regression of dendrites and motor terminals

DEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002
Laura M. Knittel
Abstract During metamorphosis of the moth Manduca sexta, an identified leg motoneuron, the femoral depressor motoneuron (FeDe MN), undergoes reorganization of its central and peripheral processes. This remodeling is under the control of two insect hormones: the ecdysteroids and juvenile hormone (JH). Here, we asked whether peripheral or central actions of the ecdysteroids influenced specific regressive aspects of MN remodeling. We used stable hormonal mimics to manipulate the hormonal environment of either the FeDe muscle or the FeDe MN soma. Our results demonstrate that motor-terminal retraction and dendritic regression can be experimentally uncoupled, indicating that central actions of ecdysteroids trigger dendritic regression whereas peripheral actions trigger terminal retraction. Our results further demonstrate that discrete aspects of motor-terminal retraction can also be experimentally uncoupled, suggesting that they also are regulated differently. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 99,116, 2002 [source]

Postpartum depression without delivering a child?

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2005
G. Manfredi
Objective:, Depression in people related to delivering women is documented in their mates, but only anecdotal in other family members. We describe a case of depression in a woman who had previously experienced postpartum depression after the birth of her nephew. Method:, A clinical description of the case. Results:, A 53-year-old woman, hysterectomized at age 47 years, was admitted for attempted suicide. She developed major depressive episode 1 month after her daughter had delivered a son. She had a past history of two postpartum depressive episodes clinically identical to the current episode. The episode resolved after 5 weeks. At 1-year follow-up, the patient is still asymptomatic. Conclusion:, Psychological and cultural factors were at play in this case more than hormonal and biopsychosocial ones. [source]

Intermediate metabolism in normal pregnancy and in gestational diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2003
G. Di Cianni
Abstract Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Gender differences in unipolar depression: an update of epidemiological findings and possible explanations

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2003
C. Kuehner
Objective: To give an update on epidemiological findings on sex differences in the prevalence of unipolar depression and putative risk factors. Material and methods: Systematic review of the literature. Results: Recent epidemiological research yields additional evidence for a female preponderance in unipolar depression, holding true across different cultural settings. Current explanations include artefacts, genetic, hormonal, psychological and psychosocial risk factors. Rather consistently, intrapsychic and psychosocial gender role related risk factors have been identified which may contribute to the higher depression risk in women. Gender role aspects are also reflected in endocrine stress reactions and possibly influence associated neuropsychological processes. Conclusion: There is a need for more integrative models taking into account psychological, psychosocial, and macrosocial risk factors as well as their interactions, which also connect these factors with physiological and endocrine responses. Furthermore, it is conceivable that across the life span, as well as across cultural settings, individual risk factors will add with varying emphasis to the higher prevalence of depression in women. [source]

Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin- and sulphonylurea-treated Type 2 diabetes

DIABETIC MEDICINE, Issue 7 2009
P. Choudhary
Abstract Aims, Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non-diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non-diabetic controls (CON). Methods, Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU-treated and 10 treated with twice-daily premixed insulin, and 10 age- and weight-matched non-diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA1c) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l. Results, Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU-treated than INS-treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups. Conclusions, Sulphonylurea-treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin-treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals. [source]

Neuropeptides and appetite control

DIABETIC MEDICINE, Issue 8 2002
J. P. H. Wilding
Abstract Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti-related protein (AGRP) and decreased levels of ,-melanocyte-stimulating hormone (,-MSH), cocaine and amphetamine-regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in bumans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes. Diabet. Med. 19, 619,627 (2002) [source]

Secondary prostatic adenocarcinoma: A cytopathological study of 50 cases

DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007
F.R.C.P.C., Kien T. Mai M.D.
Abstract Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by microscopic examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak, or focal staining in poorly differentiated PAC and in patients with prior hormonal and/or radiation therapy. The purpose of this study is to characterize the cytopathology of metastatic PAC as it has not been documented in large series. Fifty cases of metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient age was 77 ± 8 yr; serum PSA, 4.1 ± 2.3; and primary PAC Gleason score, 8.1 ± 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared with the primary PAC. In addition to the frequency of high-grade PAC, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine differentiation, are helpful features for the diagnosis of metastases of prostatic origin. Diagn. Cytopathol. 2007;35:91,95. © 2007 Wiley-Liss, Inc. [source]

Cytohormonal and morphological alterations in cervicovaginal smears of postmenopausal women on hormone replacement therapy

DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2006
Sanjay Gupta M.D.
Abstract The objective of the study was to study the cytohormonal and morphological alterations in cervicovaginal smears associated with the use of hormone replacement therapy (HRT) and to assess the utility of vaginal cytology in determining the response to HRT. Ninety postmenopausal women (30 on estrogen,progesterone combination (HRT) for 1 to 24 mo (user 1), 30 on estrogen therapy (ERT) for 1 to 44 mo (user 2), and 30 not on any hormones (nonusers)) were included in the cross-sectional study. Their lateral vaginal wall smears and cervical smears were examined for hormonal and morphological assessments, respectively. The smear pattern showed predominance of parabasal cells in 46.6% of nonusers, while none of the users had >70% parabasal cells. A high percentage (>70%) of intermediate cells was found in 46.6% of users and only in 16.6% of nonusers. A high maturation value (MV) was found in more than 75% of users but in only 16.6% of nonusers. The women with high MV (>50) were significantly less symptomatic than did nonusers. Atrophic changes were present in cervical smears of 14/20 (46.6%) nonusers when compared with 1/60 (1.66%) users. Atypical squamous cells of undetermined significance (ASC-US) were diagnosed in seven users and three nonusers. It persisted on follow-up in four users and one nonuser. Histology revealed one mild dysplasia among users. Lactobacilli were more frequently observed in users. The cytohormonal pattern on vaginal smears correlates well with the response to hormonal therapy and clinical symptoms. Awareness of the morphological alterations associated with the use of replacement hormones would enable the cytologists to reduce the false-positive diagnoses while evaluating postmenopausal smears. Diagn. Cytopathol. 2006;34:676,681. © 2006 Wiley-Liss, Inc. [source]

Effects of 4-nonylphenol on the endocrine system of the shore crab, Carcinus maenas

ENVIRONMENTAL TOXICOLOGY, Issue 3 2008
Christina M. Lye
Abstract There is a considerable body of evidence to suggest that many anthropogenic chemicals, most notably xeno-estrogens, are able to disrupt the endocrine system of vertebrates. There have been few comparable studies on the effects of exposure to these chemicals that may serve as biomarkers of endocrine disruption in aquatic invertebrate species. In addition, the evidence available is complex, conflicting, and far from conclusive. The present study aimed to investigate the impact of the xeno-estrogen 4-nonylphenol (4-NP, nominal concentrations 10,100 ,g L,1) on the regulation and functioning of the endocrine system of the shore crab Carcinus maenas. It also set out to establish whether 4-NP are causing the effects (i.e., changes of exoskeletons including secondary sexual characteristics, pheromonally mediated behavior and ecdysone levels, and the presence of vt in the male hepatopancreas) found recently in wild shore crabs (Lye et al.,2005). The study utilizes morphological (e.g., gonadosomatic and hepatosomatic indices) and hormonal (ecdysteroid moulting hormone levels and the induction of female specific proteins, vitellins) biomarkers using radioimmunoassay and an indirect enzyme linked immunosorbent assay applied to the soluble protein fraction of adult male hepatopancreatic homogenates. Exposure of C. maenas to an effective concentration as low as 1.5 ,g L,1 4-NP resulted in a reduced testis weight, increased liver weight, and altered levels of ecdysone equivalents compared to controls. Induction of vitellin-like proteins was absent in all samples tested. The ecological implications and the possible mechanisms for the action of 4-NP on the response of the shore crab to xeno-estrogen exposure are discussed. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source]

REVIEW: Stress, alcohol and drug interaction: an update of human research

ADDICTION BIOLOGY, Issue 1 2009
Magdalena Uhart
ABSTRACT A challenging question that continues unanswered in the field of addiction is why some individuals are more vulnerable to substance use disorders than others. Numerous risk factors for alcohol and other drugs of abuse, including exposure to various forms of stress, have been identified in clinical studies. However, the neurobiological mechanisms that underlie this relationship remain unclear. Critical neurotransmitters, hormones and neurobiological sites have been recognized, which may provide the substrates that convey individual differences in vulnerability to addiction. With the advent of more sophisticated measures of brain function in humans, such as functional imaging technology, the mechanisms and neural pathways involved in the interactions between drugs of abuse, the mesocorticolimbic dopamine system and stress systems are beginning to be characterized. This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from occasional drug use to drug dependence. We also review factors that contribute to different levels of hormonal/brain stress activation, which has implications for understanding individual vulnerability to drug dependence. Ultimately, these efforts may improve our chances of designing treatment strategies that target addiction at the core of the disorder. [source]

A 9-year review of dystonia from a movement disorders clinic in Singapore

EUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2006
R. D. G. Jamora
The clinical features of dystonia have not been evaluated in Southeast Asia. We therefore investigated the clinical spectrum and characteristics of dystonia in Singapore, a multi-ethnic Southeast Asian country comprising 77% Chinese, 14% Malays, and 8% Indians. We identified all dystonia patients from the Movement Disorders database and Botulinum Toxin clinic between 1995 and November 2004. Their medical records were reviewed to verify the diagnosis of dystonia and obtain demographic and clinical data using a standardized data collection form. A total of 119 (73%) patients had primary dystonia whilst 45 (27%) had secondary dystonia. There were 77% Chinese, 9% Malays, and 8% Indians. The most common focal dystonia were cervical dystonia (47%), writer's cramp (32%), and blepharospasm (11%). There was no significant difference in the distribution of dystonia between the different races. Males were noted to have earlier onset of dystonia overall. There was a significant male predominance in primary dystonia overall (M:F 1.6:1, P = 0.008) and in the subgroup of focal dystonia (M:F 1.6:1, P = 0.037). This contrasts with previous studies that found a female predominance. The role of genetic, hormonal, and environmental factors and their interactions need to be investigated to better understand the gender differences in the occurrence of dystonia. [source]

Frontiers in sebaceous gland biology and pathology

EXPERIMENTAL DERMATOLOGY, Issue 6 2008
Christos C. Zouboulis
Abstract:, The development of experimental models for the in vitro study of human sebaceous gland turned down the theory of a phylogenetic relict and led to the identification of several, unknown or disregarded functions of this organ. Such functions are the production of foetal vernix caseosa, the influence of three-dimensional organization of the skin surface lipids and the integrity of skin barrier and the influence on follicular differentiation. In addition, the sebaceous gland contributes to the transport of fat-soluble antioxidants from and to the skin surface, the natural photoprotection, the pro- and antiinflammatory skin properties and to the innate antimicrobial activity of the skin. It is mainly responsible for skin's independent endocrine function, the hormonally induced skin ageing process, the steroidogenic function of the skin as well as its thermoregulatory and repelling properties and for selective control of the hormonal and xenobiotical actions of the skin. Interestingly, sebocytes, at least in vitro, preserve characteristics of stem-like cells despite their programming for terminal differentiation. This review reports on various sebaceous gland functions, which are currently under investigation, including its role on the hypothalamus,pituitary,adrenal-like axis of the skin, the impact of acetylcholine on sebocyte biology, the activity of ectopeptidases as new targets to regulate sebocyte function, the effects of vitamin D on human sebocytes, the expression of retinoid metabolizing cytochrome P450 enzymes and the possible role of sebum as vehicle of fragrances. These multiple homeostatic functions award the sebaceous gland the role ,brain of the skin' and the most important cutaneous endocrine gland. [source]

Plasticity of human skeletal muscle: gene expression to in vivo function

EXPERIMENTAL PHYSIOLOGY, Issue 5 2007
Stephen D. R. Harridge
Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (Vmax), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing Vmax and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level. [source]

Developmental programming of obesity in mammals

EXPERIMENTAL PHYSIOLOGY, Issue 2 2007
P. D. Taylor
Converging lines of evidence from epidemiological studies and animal models now indicate that the origins of obesity and related metabolic disorders lie not only in the interaction between genes and traditional adult risk factors, such as unbalanced diet and physical inactivity, but also in the interplay between genes and the embryonic, fetal and early postnatal environment. Whilst studies in man initially focused on the relationship between low birth weight and risk of adult obesity and metabolic syndrome, evidence is also growing to suggest that increased birth weight and/or adiposity at birth can also lead to increased risk for childhood and adult obesity. Hence, there appears to be increased risk of obesity at both ends of the birth weight spectrum. Animal models, including both under- and overnutrition in pregnancy and lactation lend increasing support to the developmental origins of obesity. This review focuses upon the influence of the maternal nutritional and hormonal environment in pregnancy in permanently programming appetite and energy expenditure and the hormonal, neuronal and autocrine mechanisms that contribute to the maintenance of energy balance in the offspring. We discuss the potential maternal programming ,vectors' and the molecular mechanisms that may lead to persistent pathophysiological changes resulting in subsequent disease. The perinatal environment, which appears to programme subsequent obesity, provides a potential therapeutic target, and work in this field will readily translate into improved interventional strategies to stem the growing epidemic of obesity, a disease which, once manifest, has proven particularly resistant to treatment. [source]

Regulation of Human Myometrial Contractility During Pregnancy and Labour: Are Calcium Homeostatic Pathways Important?

EXPERIMENTAL PHYSIOLOGY, Issue 2 2001
Rachel M. Tribe
If we are to develop new strategies for the treatment and management of preterm and dysfunctional term labour, it is imperative that we improve current understanding of the control of human uterine activity. Despite many studies of animal pregnancy, there is a paucity of knowledge relating to the complex control of human myometrium during pregnancy. It is hypothesized that human myometrium is relatively quiescent during the majority of pregnancy and that as term approaches there is cascade of molecular events that prepare the uterus for labour. This review will consider the cellular mechanisms involved in the regulation of human myometrial activity and the modulation of these by hormonal and mechanical signals. In particular, the contribution of calcium homeostatic pathways to the control of human myometrial contractility during gestation will be discussed. [source]

A deficit of detoxification enzymes: pesticide sensitivity and environmental response in the honeybee

INSECT MOLECULAR BIOLOGY, Issue 5 2006
C. Claudianos
Abstract The honeybee genome has substantially fewer protein coding genes (, 11 000 genes) than Drosophila melanogaster (, 13 500) and Anopheles gambiae (, 14 000). Some of the most marked differences occur in three superfamilies encoding xenobiotic detoxifying enzymes. Specifically there are only about half as many glutathione-S-transferases (GSTs), cytochrome P450 monooxygenases (P450s) and carboxyl/cholinesterases (CCEs) in the honeybee. This includes 10-fold or greater shortfalls in the numbers of Delta and Epsilon GSTs and CYP4 P450s, members of which clades have been recurrently associated with insecticide resistance in other species. These shortfalls may contribute to the sensitivity of the honeybee to insecticides. On the other hand there are some recent radiations in CYP6, CYP9 and certain CCE clades in A. mellifera that could be associated with the evolution of the hormonal and chemosensory processes underpinning its highly organized eusociality. [source]

Is obesity protective for osteoporosis?

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2010
Evaluation of bone mineral density in individuals with high body mass index
Summary Background:, Obese individuals often present comorbidities while they appear protected against the development of osteoporosis. However, few and contradictory data are now available on skeletal modifications in obese patients. The aim of this study was to characterise bone mineral density (BMD) in overweight (BMI > 25 < 29.9) and obese (BMI > 30) patients. Methods:, We selected 398 patients (291 women, 107 men, age 44.1 + 14.2 years, BMI 35.8 + 5.9 kg/m2) who underwent clinical examination, blood tests and examination of body composition. Subjects with chronic conditions or taking medications interfering with bone metabolism, hormonal and nutritional status and recent weight loss were excluded. Results:, Interestingly, 37% (n = 146) of this population showed a significantly lower than expected lumbar BMD: 33% (n = 98) of women showed a T -score ,1.84 ± 0.71, and 45% (n = 48) of men showed a T -score ,1.88 ± 0.64. When the population was divided into subgroups based on different BMI, it was noted that overweight (BMI > 25 < 29.9) was neutral or protective for BMD, whereas obesity (BMI > 30) was associated with a low bone mass, compatible with a diagnosis of osteoporosis. No differences were observed in hormones and lipid profiles among subgroups. Conclusions:, Our results indicate that a subpopulation of obese patients has a significant low lumbar BMD than expected for age. Thus, a careful characterisation of skeletal metabolism might be useful in all obese individuals to avoid fragility fractures later in life. [source]

Intrinsic and extrinsic factors in skin ageing: a review

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2008
M. A. Farage
Synopsis As the proportion of the ageing population in industrialized countries continues to increase, the dermatological concerns of the aged grow in medical importance. Intrinsic structural changes occur as a natural consequence of ageing and are genetically determined. The rate of ageing is significantly different among different populations, as well as among different anatomical sites even within a single individual. The intrinsic rate of skin ageing in any individual can also be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible ageing of skin, also greatly increases the risk of cutaneous neoplasms. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin ageing to decreasing the genuine morbidity associated with problems of the ageing skin. A better understanding of both the intrinsic and extrinsic influences on the ageing of the skin, as well as distinguishing the retractable aspects of cutaneous ageing (primarily hormonal and lifestyle influences) from the irretractable (primarily intrinsic ageing), is crucial to this endeavour. Résumé Comme le pourcentage de la population vieillissante dans les pays industrialisés s'accroît, les préoccupations dermatologiques des personnes âgées augmentent en importance sur le plan médical. Les modifications structurelles intrinsèques sont une conséquence naturelle du vieillissement et sont génétiquement déterminées. La vitesse de vieillissement diffère significativement selon les différentes populations et selon les différents sites anatomiques, même pour un seul individu. La vitesse intrinsèque du vieillissement de la peau pour un individu peut être aussi très influencée par les facteurs personnels et environnementaux, en particulier le taux d'exposition à la lumière ultra-violette. La photodégradation qui accélère considérablement le vieillissement visible de la peau augmente également beaucoup le risque de formation de néoplasme cutané. Au fur et à mesure que la population vieillit, il faut davantage se préoccuper de diminuer la morbidité réelle associée au vieillissement de la peau, plutôt que de palier à ses conséquences cosmétiques. Il est donc crucial de s'efforcer à mieux comprendre les facteurs intrinsèques et extrinsèques qui agissent sur le vieillissement de la peau et aussi de faire la distinction entre les aspects réversibles du vieillissement cutané (facteurs essentiellement hormonaux et mode de vie) et les aspects irréversibles (principalement le vieillissement intrinsèque). [source]

Preparation and stability of cosmetic formulations with an anti-aging peptide

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1 2008
M.A. Ruiz
Wrinkling of the skin is the most obvious sign of deterioration of the human body with age. This process involves a number of genetic, constitutional, hormonal, nutritional, and environmental factors, in addition to the influence of frequently repeated facial movements during laughing, smoking, etc. This article reviews the physiological basis and mechanism of action of the active cosmetic ingredient acetyl hexapeptide-8 (Argireline®). We prepared two formulations: an emulsion with an external aqueous phase for normal to dry skin, and a gel for oily skin. Laboratory analyses, rheology tests and in vitro release assays were used to evaluate the stability of these formulations for cosmetic treatment. [source]