Evaluation of intraoperative cardiovascular responses to closed repair for pectus excavatum.

OBJECTIVE: Closed repair of pectus excavatum (PE), also known as the Nuss procedure, has become more popular recently, and whether this operation results in true cardiac improvement as opposed to postoperative physical rehabilitation or a psychological effect deserves examination. METHODS: Ten PE patients (8 males, 2 females) aged 4 to 54 years (average, 19.6+/-14 years) were prospectively evaluated using preoperative computed tomography (CT) scan, pulmonary function studies, electrocardiogram and transthoracic echocardiographic (TTE) evaluation of cardiac function. The same studies were repeated at 3 months post bar placement. In addition, intraoperative transesophageal echocardiogram (TEE) was done to measure the procedure-related values of the cardiac chamber and functional indices before and after turning of the pectus bar. RESULTS: Statistically significant changes in the pectus index, obtained by dividing the internal transverse distance of the thorax by the vertebral-sternal distance at the most depressed portion of the deformity, were noted after surgery, decreasing from 5.06+/-1.46 to 3.55+/-0.48 (P<0.05). Most patients with previously abnormal electrocardiograms showed a normal pattern after surgical repair (P<0.05). Five subjects in the PE group (50%) showed mitral valve prolapse in TTE and 4 of them had mitral regurgitation. However, these valve patterns could not be corrected after surgical repair of the chest wall deformity (P=0.25). The cardiac chamber and the function of the right ventricle were evaluated by intraoperative TEE and showed significantly increased values after retrosternal dissection and post-turning of the pectus bar. CONCLUSION: The data of this study supports the concept that closed repair directly contributes to hemodynamic improvement.

Effect of orlistat in overweight poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study.

The aim of the study was to assess the adjunctive effects of orlistat on weight loss and the influence of weight reduction on glycaemic control in overweight Chinese female type 2 diabetic patients. A randomised, placebo-controlled, double-blind, 12-week study was conducted. Chinese female type 2 diabetic patients, overweight (body mass index > 25 kg/m(2)), poorly controlled glucose levels [glycosylated haemoglobin (HbA1c) > 8%], were randomly assigned to two groups. In addition to their oral hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a placebo and the other (n = 30) received orlistat 120 mg t.i.d. for 12 weeks. Comparing the changes that occurred after 12 weeks in the orlistat and placebo groups, the former showed significantly greater reduction in bodyweight (2.5 vs. 0.4 kg; p < 0.05), fasting plasma insulin level (p < 0.01), 2-h postprandial blood glucose after glucose challenge (p < 0.01), insulin resistance (p < 0.01), HbA1c (p < 0.05), total cholesterol and triglyceride levels (p < 0.05, respectively). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of orlistat to oral hypoglycaemic agents resulted in a significant weight reduction and improvement of metabolic control in overweight Chinese female type 2 diabetic patients.

Modified Nuss operation for pectus excavatum: design for decreasing cardiopulmonary complications.

BACKGROUND: Thoracoscopic Nuss operation of funnel chest is increasingly performed. However, it has a high rate of complications. This study developed some modifications to facilitate Nuss operations with the intention of reducing several major complications. METHODS: Patients who presented for surgical repair of pectus excavatum from July 2003 through June 2004 had a preoperative computed tomography (CT) scan, pulmonary function tests, and cardiac echo before and two months after the modified Nuss operation. The following modifications of the standard Nuss procedure were implemented: (1) One small subxyphoid incision was made to guide the plate implantation and to decrease cardiopulmonary complications. (2) Thoracic muscles were dissected off the ribs to provide muscle pockets. (3) Shorter thick stainless-steel AO bars were selected to avoid thoracic outlet syndrome and restriction. (4) The bars were fixed to adjacent ribs by 4-0 stainless steel wires into the submuscular pockets. (5) No thoracoscope routinely used. (6) No chest tubes were placed to decrease chest pain or for cosmetic purposes. RESULTS: 15 patients aged between 4 and 32 years (mean, 18.6 +/- 7.8) underwent evaluation. Preoperative CT index was 4.14 +/- 0.86. The average operating time was 95.7 +/- 27.0 min. There was no bar dislocation, prolonged pain, or neuralgia. Echocardiography showed no pericarditis and no pneumothorax occurred after placement of the intrathoracic bar. CONCLUSION: A small subxiphoid incision makes bar implantation easier and has reduced the incidence of major complications in this early experience with 15 patients.

Thoracoscopic diaphragmatic repair for refractory hepatic hydrothorax: application of pleural flap and mesh onlay reinforcement.

BACKGROUND: Management of hepatic hydrothorax is difficult, and no radical treatment has been established. Based on accumulating evidence that diaphragmatic defects contribute to hepatic hydrothorax, we developed a diaphragmatic repair method for the management of this complex condition. METHODS: From October 2003 to March 2005, 10 patients (age, 32 - 83 years; 6 men and 4 women) with refractory hepatic hydrothorax (Child-Pugh class B-C) underwent thoracoscopic pleura (n = 7) or mesh (n = 3) onlay reinforcement to repair the diaphragmatic defects on which this study focuses, and all patients have since been under follow-up in a prospective observation study. RESULTS: After a mean of 7.7 months of follow-up examinations, no local recurrence occurred in all patients. Two patients died of hemorrhage from esophageal varices two months postoperatively. All patients had a better postoperative pulmonary function. CONCLUSION: The use of pleura and mesh onlay reinforcement of the diaphragm is an encouraging treatment for refractory hepatic hydrothorax.

The effect of thyroxine-suppressive therapy in patients with solitary non-toxic thyroid nodules -- a randomised, double-blind, placebo-controlled study.

The efficacy of thyroxine (T(4)) for solitary non-toxic thyroid nodule remains uncertain. In this study, 60 patients with solitary non-toxic thyroid nodule were divided randomly into two groups. Group I (n = 30) received thyroxine 100 microg/day for 6 months and group II (n = 30) received placebo. The volume of the thyroid nodules in 11 patients decreased more than 50% after thyroxine therapy (36.7%, responders). In these 11 patients, the mean serum thyroglobulin level decreased significantly (340 +/- 115 to 162 +/- 86 microg/l, p < 0.01). Compared with the non-responders (n = 19, 63.3%), the serum thyroglobulin level before treatment was significantly higher (340 +/- 115 vs. 220 +/- 102 microg/l, p < 0.05). Thyroxine-suppressive therapy is proved as a useful tool in reducing nodule size in some patients with solitary thyroid nodules. The patients with a higher serum thyroglobulin level generally respond better to thyroxine-suppressive therapy.

The relationships between insulin resistance and components of metabolic syndrome in Taiwanese Asians.

Metabolic syndrome (MetS) is a complicated clinicopathological entity with clustering of cardiovascular and metabolic risk factors, which includes central obesity, hypertension, dyslipidemia and glucose intolerance. There were many studies investigating a wide variety of clinical and pathophysiological aspects of this syndrome. However, the cutoffs of the components of MetS are not yet being evaluated by measured the insulin resistance (IR) directly. In this study, we enrolled 564 (male/female: 250/314) middle-aged healthy subjects. Each of the male and the female group was further divided into four subgroups (group 1 to group 4). Group 4 had the top 25 percentile of most severe IR determined by insulin suppression test. We then obtain the mean values of each component of the MetS in group 4 and compared them with the definitions of World Health Organization, National Cholesterol Education Program Adult Treatment Panel III, European Study Group of Insulin Resistance and International Diabetes Federation. The means of the blood pressure (BP) (male, 125/81; female, 125/80 mmHg) and the triglyceride (TG) (male, 1.6; female, 1.4 mmol/l) in group 4 were lower, and the fasting plasma glucose (6.2 mmol/l) was higher than the cutoffs of the other four sets of the criteria. The means of the high-density lipoprotein cholesterol (male, 0.9; female, 1.03 mmol/l) and the body mass index (male, 26.9; female 26.1 kg/m(2)) in group 4 were consistent with the cutoffs of other four groups and also the Taiwan Health Department criteria. In conclusion, we suggest to lower the cutoffs of the BP from 140/90 to 125/80 mmHg, TG from 1.7 to 1.6 mmol/l for males and 1.4 mmol/l for females for MetS definition, at least in Taiwan. This may help to early detect subjects under high risk of future coronary heart disease and diabetes. Still, these newly proposed cutoffs need larger-scale epidemiological studies to confirm.

Sibutramine improves insulin sensitivity without alteration of serum adiponectin in obese subjects with Type 2 diabetes.

AIM: To evaluate the effect of sibutramine on weight loss, insulin sensitivity and serum adiponectin levels in obese patients with Type 2 diabetes. METHODS: This study is a randomized, double-blind, placebo-controlled parallel comparison study of sibutramine 15 mg/day and placebo. Forty-eight eligible obese patients with Type 2 diabetes (age between 30 and 75 years with body mass index > or = 27 kg/m(2)) were randomly assigned to receive either placebo (n = 24) or sibutramine (15 mg/day) (n = 24) for 6 months. Fifteen subjects in each group underwent meal tests and modified insulin suppression tests before and after 6 months' treatment. RESULTS: After 6 months of sibutramine treatment statistically significant changes from baseline were observed for body weight (85.4 +/- 2.5 vs. 82.9 +/- 2.4 kg, P < 0.005) and body mass index (32.0 +/- 0.7 vs. 31.4 +/- 0.6 kg/m(2), P < 0.05) without a significant alteration of waist-hip ratio (W/H), blood pressure, heart rate, glycaemic parameters or lipid profiles. The steady-state plasma glucose (SSPG) level during the modified insulin suppression test was significantly reduced in the sibutramine group (17.33 +/- 2.92 vs. 14.29 +/- 4.19 mmol/l, P < 0.05) despite similar steady-state plasma insulin (SSPI) concentrations. In addition, serum adiponectin and C-reactive protein (CRP) levels remained unchanged, although modest weight reduction was achieved after sibutramine treatment. There were also no significant correlations between changes in serum adiponectin and reduction of SSPG or body weight. Daily ambient plasma insulin and glucose concentrations in response to a test meal were not significantly different in subjects receiving sibutramine treatment. CONCLUSIONS: We conclude that treatment with sibutramine 15 mg once daily effectively reduces weight and enhances insulin sensitivity without alteration of serum adiponectin levels in obese patients with Type 2 diabetes.

Metabolic characteristics in individuals with impaired glucose homeostasis.

We sought to clarify whether impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both (IFG/IGT) represent the most severe impairment in insulin resistance (IR) and insulin secretion. Among the 159 Chinese subjects, 21 were diagnosed as having IFG, 103 as having IGT and 35 as having both. IR and beta-cell function were assessed using homeostatic model assessment (HOMA) and an insulin-suppression test (IST). No differences were evident between the groups in blood pressure, body mass index, plasma insulin fasting levels and lipid profiles. However, plasma 2-h insulin levels were higher in the IGT and IFG/IGT groups. Beta-cell functions were not different between these groups. But, the result of glucose tolerance was different, in which the IFG/IGT and IFG groups displayed higher insulin sensitivity than IGT via HOMA instead of no difference via IST in the three patient groups.

Effects of sibutramine in overweight, poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study.

To assess the efficacy of sibutramine 15 mg once daily as weight reduction in overweight and obese (body mass index > 25 kg/m2) Chinese female type 2 diabetic patients and to evaluate the influence of weight loss on diabetic control, a randomised, double-blind, placebo-control, 12-week study was conducted. Chinese female type 2 diabetic patients, poorly controlled glucose levels and HbA(1C) > 8% were randomly assigned to two groups. In addition to their hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a sibutramine 15 mg once daily for 12 weeks, and the other (n = 30) received placebo for the same period. Comparing the changes that occurred after 12 weeks in the sibutramine and placebo groups, the former showed significantly greater reduction in body weight (2.5 vs. 0.1 kg, p < 0.05), fasting plasma insulin level (28.8 vs. 2.4 pmol/l, p < 0.01), 2-h postprandial blood glucose after standard test meal (3.2 vs. 1.1 mmol/l, p < 0.01), insulin resistance (5.1 vs. 0.2, p < 0.01), HbA1C (1.7% vs. 0.2%, p < 0.05), triglyceride (0.43 vs. 0.12 mmol/l, p < 0.05) and total cholesterol (0.52 vs. 0.08 mmol/l, p < 0.05). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of sibutramine to diet and oral hypoglycaemic therapy resulted in significant weight loss and improvement in metabolic parameters in the treatment group. Sibutramine should be considered for use alongside diet and oral hypoglycaemic therapy in Chinese overweight and obese women with poorly controlled type 2 diabetes.

Effect of ingestion of cow's milk hydrolysed formulas on whey protein-specific Th2 immune responses in naïve and sensitized mice.

BACKGROUND: For genetically predisposed atopic infants, cow's milk protein hydrolysed formulas have been widely used. OBJECTIVE: Whether hydrolysed formulas can induce oral tolerance to whey proteins will be extensively studied in naïve and sensitized mice. METHODS: Antigenicity of hydrolysed formulas was first studied using immunoblotting. Naïve mice fed hydrolysed formulas for 1-4 weeks were sensitized with whey allergens. In contrast, mice sensitized with whey allergens were fed hydrolysed formulas continually for 12 weeks. RESULTS: Whey allergens were found in Nan and Neoangelac FL. Large whey peptides with antigenicity were found in Nan-HA. Profound suppression of IgE, IgG1 and IgG responses to whey allergens were induced in those fed Nan for 1 week, or Nan-HA for 4 weeks. IgE responses to whey allergens were suppressed in those fed Neoangelac FL for 4 weeks, or Nan-HA for 1-2 weeks. In contrast, those fed extensively hydrolysed formulas for 1-4 weeks failed to show decreased responses. On the other hand, IgE responses to beta-lactoglobulin, but not to bovine serum albumin or alpha-lactalbumin, were decreased in sensitized mice fed Nan for 12 weeks. There was no suppression in sensitized mice fed hydrolysed formulas. CONCLUSION: Suppression of IgE responses to whey proteins was readily induced in naïve mice fed Nan or Nan-HA for 1 week. In contrast, it was hardly induced in sensitized mice even after prolonged feeding of Nan for 12 weeks, let alone hydrolysed formulas.

The effect of surgical stress on insulin sensitivity, glucose effectiveness and acute insulin response to glucose load.

Hyperglycemia after stress is a very common clinical phenomenon. It is generally hypothesized that the underlying cause is a neuroendocrine-mediated deterioration in glucose metabolism. However, the detailed roles of insulin sensitivity, glucose effectiveness and acute insulin response to glucose load in response to stress have not been well established. Hernioplasty was used as a minor stress model for studying stress-induced hyperglycemia. Eleven healthy young men were enrolled voluntarily in this study. Their mean age was 22.0 +/- 0.9 yr and BMI 23.3 +/- 0.6 kg/m2. Frequently sampled i.v. glucose tolerance tests were performed one day before and one day after the surgery. Insulin sensitivity (SI), glucose effectiveness (EG) and area under acute insulin response (AIR) were calculated from "minimal model" algorithms. We also measured fasting concentrations of human GH, ACTH and F on the days of the test. Compared to the pre-operation data, levels of ACTH and F did not change significantly after the surgery. Only GH levels were marginally significant. On the other hand, the SI (0.75 +/- 0.1, 0.52 +/- 0.9 x 10(-5) min(-1)/pmol, p = 0.04), EG (0.023 +/- 0.03, 0.016 +/- 0.003 min(-1), p = 0.01) and AIR (6738.5 +/- 1111.6, 5130.0 +/- 1047.2 pmol, p = 0.005) were all significantly decreased after surgery. The percentages of decrease were 16.3 +/- 15.5, 32.1 +/- 10.3 and 17.8 +/- 10.3%, respectively. Finally, only the changes of EG positively correlate with the changes of ACTH before and after surgery. No significant changes were noted among other stress hormones and the changes of SI, EG and AIR. In conclusion, hernioplasty results in reduced SI, EG and AIR. Among them, although not statistically significant, the EG showed the most distinct decrease after the surgery, which has not been found in previous literature.

Recombinant adeno-associated virus vector expressing glial cell line-derived neurotrophic factor reduces ischemia-induced damage.

To explore the potential of using the recombinant adeno-associated viral (rAAV) vector, expressing glial cell line-derived neurotrophic factor (GDNF) as the gene therapy for stroke, we injected rAAV vectors expressing GDNF (rAAV-GDNF) into the cortex of rats which had been experiencing transient bilateral common carotid artery ligation and right middle cerebral artery ligation for 90 min. GDNF levels in cortical tissues of rAAV-GDNF-injected animals were significantly higher than in the control animals injected with rAAV-expressing lacZ (rAAV-lacZ), indicating that rAAV can deliver and express the GDNF gene in cortical tissues. Triphenyltetrazolium chloride tissue stain analysis revealed that the rAAV-delivered GDNF gene could rescue the brain tissues from ischemia-induced injury. Cortical tissues which received rAAV-GDNF injections had both significantly smaller total volumes of infarction and smaller areas of infarction on each brain slice than those which were injected with rAAV-lacZ. An in situ labeling analysis demonstrated significantly less apoptotic cells in cortical tissues rescued by rAAV-GDNF, indicating prevention of apoptosis as the mechanism of cortical cell protection. Moreover, immunohistochemistry staining of Neu-N indicated that the rescued brain tissues contained the same number of Neu-N-positive neuronal cells as contralateral undamaged brain tissues. This provides strong evidence that cortical neuronal cells can be rescued by GDNF gene therapy. Indeed, these findings show that the rAAV is a potential delivery vector of GDNF gene for the therapy of stroke.

Resting B cells are not antigen-presenting cells in the induction of oral tolerance of specific Th2 immune responses in mice.

BACKGROUND: It has been shown that antigen presentation by resting B cells can induce tolerance to intravenously administered protein antigens, but the role of resting B cells in the induction of oral tolerance is unclear. METHODS: Mice continuously treated since birth with rabbit anti-mouse IgM serum for 5 weeks were depleted of B cells. When 4 weeks old, B cell-depleted mice drank 10% chicken egg white (EW) for 5 days. Ten weeks later, they were immunized with 10 microgram of ovalbumin in alum and their T helper 2 (Th2) immune responses were tested. RESULTS: Th2 cell-mediated IgE and IgG1 antibody responses and spleen cell production of IL-4 and IL-5 were suppressed by prior EW feeding during anti-IgM treatment. When anti-IgM-treated spleen cells collected 1 week after EW ingestion were transferred to naïve recipients, active suppression of Th2 immune responses was also demonstrated. CONCLUSIONS: Although resting small B cells aggregate in the mantle zone of follicles of intestinal Peyer's patches, the present data suggest that they are not antigen-presenting cells in the induction of oral tolerance of Th2 immune responses to oral antigens.

B-cell depletion fails to abrogate the induction of oral tolerance of specific Th1 immune responses in mice.

Antigen presentation by resting B cells has been shown to induce peripheral tolerance to intravenous (i.v.) administered soluble protein antigens. We further examined the role of resting B cells in the induction of oral tolerance. Mice were treated continuously from birth with rabbit antimouse IgM serum for 5 weeks. Immunohistological studies revealed that anti-IgM treatment depleted B cell-aggregated follicles in intestinal Peyer's patches. At 4-weeks-old, B cell-depleted mice were fed 25 mg ovalbumin or given 10% chicken egg white to drink for 5 days. Anti-IgM treatment was stopped 2 days after the last feed. Ten weeks later, the mice were immunized with 100 microg ovalbumin emulsified with complete Frund's adjuvant. Their T helper 1 (Th1) cell-regulated systemic delayed-type hypersensitivity, IgG2a antibody responses and spleen cell production of interferon-r and interleukin-2 were suppressed by prior ovalbumin or egg white feeding during anti-IgM treatment. Active suppression of Th1 immune responses was also demonstrated following adoptive transfer of egg white-fed donor spleen cells collected during anti-IgM treatment to naïve recipients. Although enormous small resting B cells are aggregated in the mantle zones of follicles of intestinal Peyer's patches, they are not the antigen-presenting cells seen in the induction of oral tolerance.

Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.

Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol.

Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios.

Urinary compound W in pregnant women is a potential marker for fetal thyroid function.

OBJECTIVE: Previously we reported 3,3'-diiodothyronine sulfate-like material (compound W) in maternal serum, and studies suggest that compound W is derived from thyroid hormones of fetal origin. In this study we characterized gestational changes of urinary compound W concentrations to correlate with changes in serum concentrations. STUDY DESIGN: Urinary samples were collected from 94 women at various gestational ages ranging from 3 to 40 weeks. Urinary compound W was first identified biochemically. The concentrations of compound W (adjusted for creatinine levels) were assessed by a 3,3'-diiodothyronine sulfate radioimmunoassay in ethanol extracts of urine samples. RESULTS: Compound W increased to 88 +/- 1.4 pmol (of 3,3'-diiodothyronine sulfate equivalent)/mmol creatinine in urinary samples obtained from 26 women in the first trimester of pregnancy compared with 40 +/- 6.9 pmol/mmol creatinine in 10 nonpregnant women. Excretion of compound W increased further during the second and third trimesters: 171 +/- 17 (n = 18) and 434 +/- 26 (n = 50) respectively. In contrast, urinary 3,3',5-triiodothyronine sulfate concentrations measured by radioimmunoassay were similar during pregnancy to values in nonpregnant women. CONCLUSIONS: Urinary compound W concentrations increase with the progression of normal pregnancy and correlate with the increase in serum levels. Random spot urine compound W concentrations, adjusted for creatinine levels, may be used in place of serum levels in conditions in which obtaining serum samples may be technically difficult, especially during population screening.

Increased urinary thyroxine sulfate excretion in thyroxine therapy.

Although increased thyroxine sulfate (T4S) levels have recently been detected in fetal serum and amniotic fluid, changes in patients in a high thyroxine (T4) state remain unclarified. This study was conducted to determine the changes in T4S in thyroid hormone regulation in women receiving suppressive T4 therapy. With a highly sensitive and specific radioimmunoassay, we measured the serum and urinary concentrations of T4S in 16 premenopausal women with benign nodular goiter before and after three months administration of T4 (3.2 micrograms/kg/day). Serum levels of other thyroid hormones were also measured. Significant increases in mean serum T4 levels post-treatment (11.1 vs. 6.6 micrograms/dL pre-treatment; P < 0.01) were found, although only low T4S levels were detectable in serum both pre- and post-T4 treatment. The mean urinary or creatinine corrected urinary T4S values post-treatment were significantly increased (20 ng/dL or 396 ng/g creatinine vs. 12 ng/dL or 174 ng/g creatinine pre-treatment, P < 0.01). There was a significant correlation between increased creatinine-corrected urine T4S and increased serum free T4. Our results indicate that the sulfation of T4 may be related to the regulation of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia.

Reversal of the temperature-shift-induced growth restriction of a temperature-sensitive simian virus 40 T-antigen-transformed human fibroblast cell line by treatment with retinoic acid.

We previously established a human fibroblast cell line, HFL 6-2, that contains a temperature sensitive simian virus 40 (SV40) T antigen, permitting cell growth at 35 degrees C but restricting growth at 39 degrees C. p21 (Waf1/Cip1) was significantly induced by temperature shifts in HFL 6-2 cells. Here we show that all-trans-retinoic acid (RA) treatment prevented the growth restriction of HFL 6-2 cells at 39 degrees C. In the presence of RA, HFL 6-2 cells proliferated into sizeable colonies even at 39 degrees C. [3H]Thymidine incorporation and flow cytometry analysis revealed that cells exposed to RA maintained DNA synthesis at 39 degrees C. Prevention of growth restriction by RA was correlated with a lack of induction of p21 at the transcription level. These observations suggest that RA may prevent the senescence process by repressing p21 gene expression, and perturb the growth regulation of somatic cells.

Maturation of hepatic desulfation activity in developing rats.

The present study was carried out to further characterize the maturation of desulfation activity in developing rats. High levels of 3,3',5-triiodothyronine sulfate (T3S) were found in rat fetal serum whereas 3,3',5-triiodothyronine (T3) levels were low. The ratio of T3S/T3. was dramatically reversed in the rat maternal circulation. Maternal rats had higher desulfation activity than did near-term fetuses. Desulfation of T3S to T3 by microsomes of fetal and maternal livers were studied by incubating microsomes with T3S as a substrate. Desulfated T3 was measured by radioimmunoassay. The Km and Vmax values for desulfation of T3S to T3 by hepatic microsomes in different age groups were compared. Little desulfation activity was found in hepatic microsomal preparations from fetal rats compared with newborn rats. There was a trend of increasing desulfation activity in rats after birth until 1 month of age, although this was not significant. A surge of desulfating activity was observed between the 1- and 2-month old groups. The K(m) values for T3S desulfation activity were similar in all age groups. The Vmax values for the T3S to T3 desulfation activity progressively increased after birth until 2 months of age. The Vmax of the latter group, however, was comparable to that of the maternal group. These results suggest that the maturation of desulfation activity in the microsomal preparations from rat livers is completed by 2 months of age and is mainly due to increased enzyme capacity. Sulfation-desulfation of T3 may play a role in the thyroid hormone regulation of developing mammals.