Lipoprotein lipase but not hormone-sensitive lipase activities achieve normality after surgically induced weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is currently the most common practice for inducing weight loss in morbidly obese patients (BMI>40 kg/m2), its effect on the lipid content of adipose tissue and its lipases (lipoprotein lipase [LPL] and hormone-sensitive lipase [HSL]) are controversial. METHODS: We analyzed LPL and HSL activities and lipid content from plasma as well as subcutaneous (SAT) and visceral (VAT) adipose tissue of 34 morbidly obese patients (MO) before and after (6 and 12 months) Roux-en-Y gastric bypass surgery and compare the values with those of normal weight (control) patients. RESULTS: LPL activity was significantly higher in MO (SAT=32.9+/-1.0 vs VAT=36.4+/-3.3 mU/g tissue; p<0.001) than in control subjects (SAT=8.2+/-1.4 vs VAT=6.8+/-1.0 mU/g tissue) in both adipose depots. HSL activity had similar values in both types of tissue (SAT=32.8+/-1.6 and VAT=32.9+/-1.6 mU/g) of MO. In the control group, we found similar results but with lower values (SAT=11.9+/-1.4 vs VAT=12.1+/-1.4 mU/g tissue). Twelve months after surgery, SAT LPL activity diminished (9.8+/-1.4 mU/g tissue, p<0.001 vs morbidly obese), while HSL (46.6+/-3.7 mU/g tissue) remained high. All lipids in tissue and plasma diminished after bariatric surgery except plasma nonesterified fatty acids, which maintained higher levels than controls (16+/-3 vs 9+/-0 mg/dL; p<0.001, respectively). CONCLUSIONS: When obese patients lose weight, they lose not only part of the lipid content of the cells but also the capacity to store triacylglycerides in SAT depots.

Ghrelin and apolipoprotein AIV levels show opposite trends to leptin levels during weight loss in morbidly obese patients.

BACKGROUND: Although bariatric surgery is the most common procedure used to induce weight loss in morbidly obese patients, its effect on plasma satiety factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim of this work was to analyze these parameters before and at different times after surgery. METHODS: Plasma was obtained from 34 patients before undergoing Roux-en-Y gastric bypass and during weight loss in the 12 months following surgery. RESULTS: Morbidly obese patients had significantly higher values (147%) of leptin than normal-weight (NW) persons, while their ghrelin levels were 46% less than NW. Apo-AIV levels had approximately the same value in both groups (obese and NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%. Both parameters reached values less than or near NW, respectively, at 1 year after surgery. During the first month after surgery, apo-AIV plasma levels decreased (47%) but later increased and finally returned to preoperative values. Apo-AIV levels were correlated negatively with leptin and positively with ghrelin. High-density lipoprotein (HDL) levels were positively correlated with those of ghrelin and apo-AIV. CONCLUSIONS: During weight loss, plasma leptin and ghrelin could be good markers of total fat decrease. Ghrelin could also indicate gastric mucous improvement, whereas apo-AIV could indicate the recovery of intestinal function. Changes produced in the HDL levels of morbidly obese patients during weight loss suggest a decreased risk of coronary disease.

CSF galanin and cognition after shunt surgery in normal pressure hydrocephalus.

BACKGROUND: "Normal" pressure hydrocephalus (NPH) is associated with injury to neurotransmitter and neuropeptide systems that recovers after surgery. This could be linked to changes in galanin, a neuropeptide with inhibitory effects on basal forebrain cognitive function. OBJECTIVE: To examine changes in CSF galanin concentrations in patients with normal pressure hydrocephalus undergoing shunt surgery, and to investigate the relation between these changes and cognitive functioning. METHODS: Eight patients underwent surgery for idiopathic normal pressure hydrocephalus. Lumbar CSF galanin determinations, cognitive status, and clinical status were quantified before operation and six months after. Cognition was assessed by an extensive battery of tests measuring attention, memory, speed of mental processing, visuospatial function, and frontal lobe function. RESULTS: CSF galanin concentration decreased after surgery. This reduction correlated with improved clinical and cognitive functioning, specifically with attention and visuomotor speed, visuoconstructive and frontal functioning, and clinical status according to the NPH scale, including the sphincter and cognitive components. CONCLUSIONS: The cognitive and clinical improvement after shunt implantation correlated with CSF galanin levels, suggesting that the distribution or function of this agent involves cerebral structures that have some potential for recovery. In this study, galanin was related to several cognitive functions that may be associated with the fronto-subcortical deficits underlying cognitive dysfunction in normal pressure hydrocephalus.

Shunt related changes in somatostatin, neuropeptide Y, and corticotropin releasing factor concentrations in patients with normal pressure hydrocephalus.

OBJECTIVES: Recent data indicate that alterations in brain neuropeptides may play a pathogenic role in dementia. Neuropeptide Y (NPY), somastostatin (SOM), and corticotropin releasing factor (CRF) are neuropeptides involved in cognitive performance. Decreased SOM and NPY concentrations have been found in patients with normal pressure hydrocephalus and are probably the result of neuronal dysfunction, which could potentially be restored by shunting. The effects of shunt surgery on preoperative SOM, NPY, and CRF concentrations were studied. Any improvements in neuropeptide concentrations that could lead to clinically significant neuropsychological and functional changes were also investigated. METHODS: A prospective study was performed in 14 patients with normal pressure hydrocephalus syndrome with a duration of symptoms between 3 months and 12 years. Diagnosis was based on intracranial pressure (ICP) monitoring and CSF dynamics. Concentrations of SOM, NPY, and CRF in lumbar CSF were determined before shunting and again 6-9 months after surgery. A battery of neuropsychological tests and several rating functional scales were also given to patients before and after shunting. RESULTS: After shunting, SOM and CRF concentrations were significantly increased in all patients. Concentrations of NPY were increased in 12 of the 14 patients studied. The clinical condition of 13 of the 14 patients was significantly improved 6 months after surgery. This improvement was more pronounced in gait disturbances and sphincter dysfunction than in cognitive impairment. No significant differences in any of the neuropsychological tests were seen for the group of patients as a whole despite the increased neuropeptide concentrations. CONCLUSIONS: Shunting can restore SOM, NPY, and CRF concentrations even in patients with longstanding normal pressure hydrocephalus. However, despite the biochemical and clinical improvement in some areas such as ambulation and daily life activities, cognitive performance did not significantly improve. The role of neuropeptides in the diagnosis and treatment of patients with normal pressure hydrocephalus syndrome is discussed.

[Subarachnoid hemorrhage, cerebral ischemia and endothelin-1]. / Hemorragia subaracnoidea, isquemia cerebral y endotelina-1.

INTRODUCTION: Cerebral vasospasm is involved in the development of delayed ischemic lesions in patients with subarachnoid hemorrhage. We developed an integral theoretical model to explain the pathophysiology of cerebral vasospasm, in which endothelin-1 has a pivotal role in the development of both cerebral vasospasm and delayed ischemic neurological deficits (DIND). OBJECTIVE: The objective of this study is to analyze the relationship between temporal profile of plasma endothelin-1 levels and the development of cerebral vasospasm and DIND. PATIENTS AND METHODS: We analyzed sequentially plasma endothelin-1 levels in 17 patients with aneurysmatic subarachnoid hemorrhage. All the patients had complete clinical and neuroradiological studies. Patients were classified according to Fisher's score. RESULTS: Patients (4 males and 13 females, aged 48.1 +/- 20.3 years) had a good clinical condition (Hunt-Hess < 4, GCS > 10). Two weeks after bleeding, patients had higher plasma endothelin-1 levels than healthy volunteers (p = 0.024). Patients who developed DIND had higher plasma endothelin-1 levels (p = 0.034) and a different evolution (p = 0.0146) than patients without DIND. There is a significant correlation (p = 0.02) between basal plasma endothelin-1 levels and GOS score. Multiple regression analysis shows a significant dependence between plasma endothelin-1 levels and Fisher's score (p = 0.0195), development of DIND (p = 0.0095), and GOS score (p = 0.0319). Logistic regression analysis finds a predictive relation between Fisher's score and plasma endothelin-1 levels for the development of DIND (overall predicted = 74.24%; p = 0.0148). CONCLUSIONS: Plasma endothelin-1 levels are increased in patients after subarachnoid hemorrhage and are associated with the development of cerebral vasospasm and DIND.

Plasma corticotropin-releasing factor in depressive disorders.

BACKGROUND: The aim of this work was to investigate alterations of plasma corticotropin-releasing factor (CRF) levels in depressive states. We have also measured plasma cortisol and corticotropin (ACTH) concentrations and examined their correlation with the peripheral CRF values. METHODS: Thirty-six outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having major depressive disorder (n = 26) and dysthymic depressive disorder (n = 10) were studied. Among the major depressed patients, 10 suffered from severe depressive disorder and 16 from mild or moderate depressive disorder. The comparison group consisted of 17 healthy volunteers. Cortisol, ACTH, and CRF concentrations were determined by iodine-125 radioimmunoassay; CRF measurements were performed on C18 extracted samples. RESULTS: CRF and cortisol plasma concentrations were significantly higher in major depression and dysthymia than in the comparison group. The major depressed patients did not show significantly different CRF and cortisol levels than the dysthymic. Severe major depressive disorder exhibited significantly higher CRF plasma levels than the mild or moderate episodes. Plasma cortisol and CRF concentrations correlated significantly. CONCLUSIONS: The results obtained indicate that plasma CRF values are altered in depressive disorders and suggest that these determinations could be important for understanding the pathophysiology in affective illness.

Decreased cholecystokinin levels in cerebrospinal fluid of patients with adult chronic hydrocephalus syndrome.

Cholecystokinin (CCK) levels were measured in cerebrospinal fluid (CSF) of patients with adult chronic hydrocephalus syndrome (ACHS) (n = 16) and compared with levels from a control group (n = 11). The CSF concentration of CCK in the ACHS group (0.79 +/- 0.53 fmol/mL) was significantly reduced (p = .002) with respect to the controls (1.55 +/- 0.54 fmol/mL). As CCK-8, the most prevalent from of CCK in the central nervous system, has been demonstrated to play a significant role in several physiological and behavioral actions, the reduced octapeptide values found in ACHS could be involved in the disturbances associated with this disorder. Continuous monitoring of intracranial pressure (ICP) demonstrated different ICP profiles in ACHS. We found that all patients with abnormal ICP records except one showed CCK values under the detection limit. Three of the 4 patients with normal ICP had CCK levels within the normal range. These preliminary studies could evidence that ICP alterations are responsible for part of the loss of brain neuropeptide levels in ACHS.

Epidermal growth factor excretion in burned rats.

Evidence for epidermal growth factor (EGF) involvement in the physiological response to burns was sought from urinary levels of EGF, urea and creatinine in male rats using a standardized thermal skin injury model (25 per cent body surface) and treated with fluid resuscitation. Postmortem, the skin lesions were studied by microscopy to guarantee the absence of inflammatory complications. Statistically significant differences were observed in body weight, urea and creatinine excretion when compared to the basal values. When EGF excretion results were evaluated as raw data (expressed as ng/mg of creatinine or ng/day) compared to basal levels, no statistically significant differences were observed. However, when the results were expressed as percentage increases with respect to the basal values, a statistically significant increase was found over the first 7 days postinjury (P = 0.029).

Neurokinin concentrations in cerebrospinal fluid. A preliminary study in Parkinson's disease.

Immunoreactive neurokinin A was measured in the cerebrospinal fluid of twelve patients with Parkinson's disease and eleven normal subjects, using a sensitive and precise extraction/concentration radioimmunoassay method. The mean value obtained in Parkinson's disease patients (13.2 +/- 4.6 pmol/l) was lower than that of the controls (17.4 +/- 5.9). The tendency toward a significant decrease (p = 0.085) found in this preliminary study could indicate that neurokinin A containing neurons are involved in the pathophysiology of Parkinson's disease. In addition, the establishment of reference values for neurokinin A in cerebrospinal fluid may provide a basis for further studies of this neuropeptide in neurological disorders.

Somatostatin cerebrospinal fluid levels in dementia.

Somatostatin levels were measured in cerebrospinal fluid of patients with Alzheimer's disease, multi-infarct dementia and normal pressure hydrocephalus and compared with levels from a normal control group. All pathological groups showed a statistically significant decrease of somatostatin with respect to the control group, but no significant differences were found amongst them. A negative correlation was found between the Mini Mental State Test and the somatostatin levels in Alzheimer's disease patients but not in the other groups. Our results confirm that the lower levels of somatostatin in cerebrospinal fluid are not specific to Alzheimer's disease and indicate that the decrease found in all the groups is probably the result of neuronal destruction or damage in the diseases examined.

Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST.

OBJECTIVE: The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels. METHOD: Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents. RESULTS: Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects. CONCLUSIONS: These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.

Stability of somatostatin in total parenteral nutrition.

The stability of somatostatin, added to a total parenteral nutrition formula, in glass containers and in plastic ethylene vinyl acetate containers was investigated. The somatostatin concentration decreased immediately from 3 micrograms/ml to 0.3-0.6 micrograms/ml after addition to the emulsion. In spite of this rapid decrease, somatostatin concentrations remained stable with values of 0.4-0.7 micrograms/ml during the follow-up period (24 h). These findings could be explained assuming adsorption to the surface of the container.

Cerebrospinal fluid neuropeptide Y in Alzheimer's disease.

The cerebrospinal fluid neuropeptide Y level was measured by radioimmunoassay in 20 patients with probable Alzheimer's disease and in 19 controls. The mean level was lower in patients (69.5 +/- 36.7 pg/ml) than in controls (103 +/- 21.8 pg/ml; p less than 0.001). Patients with a disease duration of greater than 2 years had cerebrospinal fluid neuropeptide Y levels lower than those with shorter disease duration (p less than 0.02). These results suggest that neuropeptide Y containing cells may be involved in Alzheimer's disease. No correlation was found between neuropeptide Y levels and degree of cognitive impairment or age at disease onset.

Correlation between plasma estradiol and estrone-3-glucuronide in urine during the monitoring of ovarian induction therapy.

An improved radioimmunoassay was developed to determine estrone-3-glucuronide in daily urine. Resulting levels were compared with those of estradiol in plasma of 10 healthy women and 14 undergoing ovulation induction therapy with human menopausal gonadotropin and human chorionic gonadotropin. A highly significant correlation between plasma estradiol and urinary estrone-3-glucuronide in normal (r = .9209; P less than .01) and stimulated (r = .9229; P less than .01) women was demonstrated. These results proved that the pattern of excretion of estrone-3-glucuronide perfectly reflected the changes in plasmatic estradiol levels when monitoring ovarian induction and that estrone-3-glucuronide determinations can provide clinically useful information in human induction therapy.

Plasma levels of beta-endorphin, cortisol, prolactin and growth hormone in depressed patients.

Basal serum cortisol, growth hormone, prolactin and immunoreactive (IR) plasma beta-endorphin levels were measured in 31 depressed patients (14 endogenous, 17 nonendogenous) undergoing the dexamethasone suppression test. The endogenously depressed patients had significantly higher (22.55 +/- 1.34 micrograms/dl) predexamethasone cortisol levels than the nonendogenous patients (16.34 +/- 1.93 micrograms/dl). The mean serum prolactin and growth hormone values of these two groups were not significantly different, while plasma IR-beta-endorphin levels of the endogenous group (40.11 +/- 3.57 pg/ml) were significantly lower than those of the nonendogenous group (120.33 +/- 27.98 pg/ml). Neither group showed a significant correlation between plasma IR-beta-endorphin and serum cortisol values. These results indicate that measurement of predexamethasone serum cortisol values and plasma IR-beta-endorphin could be valuable laboratory tests in the diagnosis of depression.

Salivary testosterone levels in infertile men.

Salivary testosterone levels were measured in 18 normal men, 29 oligospermic and six azoospermic subjects, using a specific and sensitive radioimmunoassay (RIA). There was a significant reduction (P less than 0.001) in salivary testosterone levels in the group of oligospermic (0.266 +/- 0.086 nmol/l) and azoospermic (0.234 +/- 0.055 nmol/l) subjects when compared with controls (0.348 +/- 0.070 nmol/l). A good correlation was found between salivary and plasma testosterone levels in normal (r = 0.62, P less than 0.01) and infertile men (r = 0.58, P less than 0.01). This study demonstrates that salivary testosterone levels, a non-invasive means of sample collection, may be used for evaluation of androgen status in male infertility.

Hormonal profile and serum zinc levels in uraemic men with gonadal dysfunction undergoing haemodialysis.

Serum gonadal hormones, gonadotrophins and zinc levels were studied in thirteen men aged 29-62 yr with chronic renal failure undergoing haemodialysis. All patients had decreased libido and impotence. Serum testosterone levels in patients (18.5 +/- 1.3 (SEM) nmol/l) were significantly lower (p less than 0.05) than in the control group (24.1 +/- 2.2 (SEM) nmol/l) although salivary testosterone levels were strictly within the normal range. Mean serum 17-beta-oestradiol and luteinizing hormone levels (0.19 +/- 0.03 (SEM) nmol/l, and 57.4 +/- 13.1 (SEM) IU/l, respectively) were significantly higher (p less than 0.05 and p less than 0.005, respectively) than in the control group (0.11 +/- 0.02 (SEM) nmol/l and 14.8 +/- 1.9 (SEM) IU/l, respectively). Mean progesterone and follicle-stimulating hormone levels in patients were not significantly different from those of control subjects. Mean prolactin values in patients (1,019 +/- 285 (SEM) mIU/l) were significantly higher (p less than 0.01) than in the control group (211 +/- 24 (SEM) mIU/l). Serum prolactin levels in five patients were extremely high (above 1,200 mIU/l). There was no statistically significant difference in serum zinc levels between patients and controls. As salivary testosterone is normal, it seems that hyperprolactinaemia and raised serum 17-beta-oestradiol levels may be responsible, at least in part, for sexual dysfunction in male patients with chronic renal failure receiving haemodialysis.