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Biomedical subjects

J Guechot

Publications and source records attributed to J Guechot.

16 recordsLinked to original sources
PubMed2002

Design of poly-epsilon-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery.

This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.

Adhesives↗
PubMed2000

Hyaluronidase activity in serum of patients with monoclonal gammapathy.

Hyaluronidase and hyaluronic acid, two substances thought to be strongly implicated in carcinogenesis, were assessed in the plasma of 35 patients with newly documented monoclonal gammapathy and in 25 control patients. A significant increase was found in plasma hyaluronidase activity in the patients with monoclonal gammapathy. A statistically significant positive correlation was found between hyaluronidase activity and monoclonal immunoglobulin levels in plasma. An increase in serum hyaluronidase activities may be a response to the deleterious effect of hyaluronic acid in cell migration and tumor progression. Further studies are needed to assess the value of hyaluronidase activity as a marker of tumor progression.

Aged↗
PubMed1998

Seminal androgen concentrations and residual sperm cytoplasm.

To explore a possible link between seminal androgen concentrations and residual sperm cytoplasm, which constitutes one of the cytological anomalies of the spermatozoon middle piece, testosterone (T), delta4-androstenedione, the precursor of T during testicular androgen biosynthesis and the active metabolite of T, dihydrotestosterone, were assayed in the seminal fluid of 37 patients. A statistically significant correlation was found by linear regression (r = +0.380, P = 0.020, y = 0.02x + 0.45) between seminal T concentrations and the percentage of spermatozoa with a residual cytoplasmic droplet. Given the impact on fertility of residual sperm cytoplasm, assessment of seminal T concentrations could provide useful information on the fertility status of patients.

Adult↗
PubMed1997

Evidence for a deficiency of interferon response in mononuclear cells from hepatitis C viremic patients.

BACKGROUND/AIMS: The pathophysiology of chronic hepatitis C and the mechanisms of resistance to interferon alpha are poorly understood. The aim of this work was to assess the influence of HCV infection and the viral genotype on lymphocyte production of 2',5' oligo-adenylate synthetase activity and monocyte production of TNF alpha and IL1 beta. METHODS: Mononuclear cells from 50 consecutive patients were studied after 6 months of interferon treatment. Patients with persistent viremia (PCR-positive, elevated ALT, n = 39) were compared with the PCR-negative patients with normal ALT activity (n = 11) of similar age and sex ratio. RESULTS: Cells from the viremic patients showed lower basal and stimulated 2',5' oligo-adenylate synthetase activity, and a lower in vitro response capacity to human recombinant interferon. In contrast, no difference was observed in basal and stimulated TNF alpha or IL1 beta production between the two groups. In the PCR-positive patients the viral genotype had no significant influence on the response of mononuclear cells to interferon or endotoxin. CONCLUSIONS: These results show that the presence of HCV in blood is associated with an elective defect in interferon system activation, independently of the viral genotype.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

[Fibronectin and hyaluronic acid in seminal fluid: relationship with sperm count and percentage of typical forms].

Two components of the extra cellular matrix, hyaluronic acid (HA) and fibronectin (Fbn), were assessed in the seminal fluids of 29 patients submitted for diagnosis of infertility. The concentrations of HA and Fbn were elevated in seminal plasma in comparison to their ranges of concentration in normal sera. No correlations were found between seminal Fbn and sperm count per ml and/or ejaculate, normal sperm cytology and multiple anomaly index (MAI). The concentrations of HA were negatively correlated with sperm count per ml (p < 0.01, r = -0.5) and ejaculate (p < 0.005, r = -0.5), and also with sperm cytology (p < 0.001, r = -0.6). A positive correlation was found between seminal concentrations of HA and MAI (p < 0.001, r = +0.7). It seems that high seminal HA concentrations were in relation with the bad results of sperm count and sperm cytology. These data suggest that spermatozoon could be implicated, in part, in the seminal HA metabolism.

Fibronectins↗
PubMed1994

Cytokine response to burn injury: relationship with protein metabolism.

Plasma levels of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL-6), and markers of protein metabolism were determined in 12 burn patients throughout the healing period (day 2 to 21 post-injury) to determine the pattern of variations in plasma cytokine concentration. To establish the relationship between cytokine production and the nutritional status a wide range of severity standpoints (burn surface area ranging from 9% to 82%) was chosen. Interleukin 6 levels were increased in all patients throughout the study period; maximum concentrations (615 +/- 198 pg/mL) were reached on day 4 and correlated (p < 0.01) with the extent of burn injury. Tumor necrosis factor alpha levels were also elevated; they were significantly higher on day 7 in the patients who developed sepsis than in the other patients (67 +/- 21 pg/mL vs. 20 +/- 7 pg/mL; p < 0.05) but did not correlate with the extent of burn injury. Interleukin 1 beta was rarely detected. Cortisolemia on day 7 was inversely correlated with levels of TNF alpha but not with those of IL-6. Interleukin 6 levels correlated positively with protein turnover (phenylalaninemia) and catabolism (3-methylhistidine/creatinine ratio) and negatively with levels of fibronectin and transthyretin. Our data indicate that the systemic cytokine response to burn injury is mainly represented by IL-6. These data also support the hypothesis that IL-6 is a key mediator of the variations in protein metabolism following burn injury.

Adult↗
PubMed1992

Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes.

Cell-mediated immunity and macrophage activity, especially that of Kupffer cells, are impaired during cholestasis. Some evidence exists that bile acids play a role in these immune defects. The purpose of this study was to evaluate the effects of individual bile acids on immunity and to determine whether monocytes could be a target. We assessed the effects of chenodeoxycholic acid, an endogenous bile acid, ursodeoxycholic acid, which has been shown to partially correct the immunological abnormalities observed in primary biliary cirrhosis, and their tauroconjugates on the production of interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Chenodeoxycholic acid had a dose-dependent inhibitory effect on interleukin-1 (inhibitory concentration 50% = 60 mumol/L), interleukin-6 (inhibitory concentration 50% = 80 mumol/L) and tumor necrosis factor-alpha (inhibitory concentration 50% = 80 mumol/L) production; inhibition was almost complete at 250 mumol/L. In contrast, ursodeoxycholic acid had lesser or minimal inhibitory effects (inhibitory concentration 50% = 100 mumol/L for interleukin-1 and above 200 mumol/L for interleukin-6 and tumor necrosis factor-alpha). The inhibitory effects of taurochenodeoxy-cholic acid and tauroursodeoxycholic acid were similar to those of chenodeoxycholic acid and ursodeoxycholic acid, respectively. Ursodeoxycholic acid did not reverse the chenodeoxycholic acid-induced inhibition of interleukin-6 or tumor necrosis factor-alpha production. In conclusion, chenodeoxycholic acid exerts strong inhibitory effects on monocyte activity in vitro, whereas the effects of ursodeoxycholic acid are minor.

Cell Survival↗
PubMed1991

Effect of dihydrotestosterone on the rate of ethanol elimination in healthy men.

Testosterone (T) and, more potently, dihydrotestosterone (DHT), are in vitro inhibitors of hepatic alcohol dehydrogenase (ADH). An increase in the rate of ethanol disappearance (RED) in man has been observed after orchidectomy. We thus investigated the influence of DHT administration on RED in 10 healthy male volunteers. RED was estimated after an oral ethanol bolus (0.6 g/kg), before and after a 14-day treatment with DHT (2 x 125 mg per day percutaneously; Andractim, Besins iscovesco, France). A mean 11.5-fold increase in DHT levels and a 2.0-fold decrease in T values were observed after DHT administration, confirming the good compliance with treatment. RED was decreased after DHT (0.168 +/- 0.043 vs. 0.137 +/- 0.043 g/l/hr; mean +/- SD; p less than 0.01 using Wilcoxon's paired comparison test). These data are consistent with a DHT-induced inhibition of hepatic ADH in vivo. This could have a beneficial effect by decreasing acetaldehyde production in alcoholic patients, in whom marked hypoandrogenism frequently occurs.

Administration, Cutaneous↗
PubMed1989

Evidence of the intact hepatocyte theory in alcoholic cirrhosis.

To improve our understanding of the predominant operational model involved in the decreased clearance in cirrhosis, hepatic clearance, the extraction ratio of indocyanine green, and liver plasma flow were estimated in cirrhosis, either with a method based on the Fick principle or with a pharmacokinetic method assuming a bicompartmental plasma elimination of the dye. The two methods gave similar values for clearance. In contrast, the pharmacokinetic analysis gave significantly (p less than 0.01) lower hepatic plasma flow values and significantly (p less than 0.01) higher extraction values than those obtained with the reference (Fick principle) method. The main finding of this work is that in these cirrhotic patients, as in normal subjects, 'cellular' extraction estimated by the pharmacokinetic method is in the range of 0.60-0.80, whereas the extraction by the entire liver, assessed by the reference method, is low. In chronic liver diseases such as cirrhosis these data support the predominance of the intact hepatocyte theory, which assumes the existence of intrahepatic shunts associated with normally perfused and normally extracting hepatocytes. In acute liver disease, a cellular damage could be superadded.

Adult↗
PubMed1987

Hepatic uptake of sex steroids in men with alcoholic cirrhosis.

We attempted to determine to what extent the degree of liver function impairment might affect the hepatic uptake and, as a consequence, alter the systemic plasma levels of endogenous sex steroids in male patients with alcoholic cirrhosis. The plasma levels and hepatic uptake of the steroids dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, progesterone, and 17-hydroxyprogesterone were assessed. Systemic plasma levels of testosterone and dehydroepiandrosterone were significantly (p less than 0.05) reduced, whereas those of androstenedione, estrone, and estradiol were significantly (p less than 0.05) elevated in men with alcoholic cirrhosis when compared to controls. Sex hormone binding globulin levels were also significantly elevated (p less than 0.01). The hepatic uptake of sex steroids depended on the degree of liver function impairment as shown by the linear significant relationship between their hepatic extractions and that of indocyanine green (r = 0.74-0.92, p less than 0.05; except for dihydrotestosterone, r = 0.17, not significant). In addition, the hepatic uptake of sex steroids depended on the binding affinity to sex hormone binding globulin. The higher the affinity for sex hormone binding globulin, the lower the hepatic uptake influenced by liver function impairment. It was estimated that hepatic clearances accounted for only 20%-50% of the metabolic clearance of sex steroids. No significant relationship between plasma levels of sex steroids and their hepatic clearance was found. We show here that in alcoholic cirrhosis the extent of hepatic uptake of sex steroids depends partly on the degree of liver function impairment and partly on the degree to which they are bound to sex hormone binding globulin. Production rate or peripheral metabolism, or both, rather than hepatic uptake alone may account for the altered circulating levels of sex steroids.

Adult↗
PubMed1986

Myoglobinemia after burn injury: relationship to creatine kinase activity in serum.

Myoglobin is released into the blood after burn injury. We measured it and other analytes in blood collected from 22 burn patients two to seven times during their recovery. There was a significant correlation between myoglobinemia and creatine kinase (CK) activity in serum (r = 0.764; p less than 0.001). In a group of 14 thermal-burn subjects a correlation was found between burn depth (clinically expressed as Unit Burn Surface) and both myoglobinemia (r = 0.825; p less than 0.01) and CK activity (r = 0.686; p less than 0.01). In eight thermal-burn patients who were recovering satisfactorily, myoglobin and CK activity measured on days 2, 4, 7, 10, and 13 after injury were significantly increased (p less than 0.05) on days 2, 4, and 7. Evidently myoglobinemia and CK activity are good biological markers of burn depth, and reflect muscle damage equally well.

Burns↗
PubMed1985

[Radioimmunoassay of salivary l7 alpha-hydroxyprogesterone. Values obtained in healthy subjects and in patients treated for congenital hyperplasia of the adrenal glands].

The authors describe a method for the radioimmunoassay of 17 alpha-hydroxyprogesterone in the saliva. The limit of detection is 1.96 fmole/tube. Salivary 17 alpha-hydroxyprogesterone was measured in control subjects. Values found were of 296 +/- 115 pmol/l in the male, and 251 +/- 23 pmol/l in the female during the follicular phase and 401 +/- 94 pmol/l during the luteal phase, and 115 +/- 30 pmol/l in the prepubertal child. Concentrations were much higher in the newborn and decreased during the first days of life. Variations in salivary concentrations were compared with those in plasma 17 alpha-hydroxyprogesterone during the 24-hour period and with the Synacthene stimulation test. The excellent correlation (r = 0.0969) between salivary 17 alpha-hydroxyprogesterone and plasma 17 alpha-hydroxyprogesterone in 28 patients being treated for 21 hydroxylase deficiency makes it possible to suggest salivary assay in place of plasma assay in the therapeutic follow-up of such patients.

17-alpha-Hydroxyprogesterone↗
PubMed1984

[Plasma and saliva DST (dexamethasone suppression test) in depression. Clinical applications and kinetic approach].

Both plasmatic and salivary DST were simultaneously performed on a sample of 37 patients with a diagnosis of major depressive disorder (DMS III criteria): 22 primary depressions and 15 secondary depressions. Salivary DST showed a similar specificity but a decreased sensitivity in comparison with plasmatic DST. Essentially, the simultaneous use of both tests resulted in a better specificity for primary depression.

Adult↗
PubMed1982

Physiological and pathological variations in saliva cortisol.

A radioimmunological method for measuring saliva cortisol was worked out. It includes one extraction and one radiocompetitive reaction with an anticortisol 3-CMO:BSA immunoserum. Frequent values for saliva cortisol were determined in various physiological and pathological conditions and compared to plasma cortisol values. In adult men, the mean concentrations at 8 a.m. and midnight were respectively 14.50 +/- 7.10 and 1.40 +/- 1.21 nmol/l (mean +/- SD). In untreated women, plasma and saliva cortisol levels were not significantly different from those measured in women taking estroprogestative drugs or in pregnant women. Following stimulation by synthetic beta 1-24 ACTH (Synacthen), the saliva cortisol determined 90 min after the 8 a.m. sampling rose by over 500% whereas plasma cortisol only rose by 120%. Similarly the drop in 8 a.m. cortisol, which followed midnight administration of 1 mg of dexamethasone was larger for saliva than for plasma cortisol. In patients with adrenal hyperactivity the circadian rhythm disappeared from saliva cortisol and patients with deficient adrenal activity displayed drastically reduced levels for saliva cortisol. Saliva cortisol seems thus to be more helpful to diagnosis than plasma cortisol.

Adolescent↗