High salt exacerbates programmed hypertension in maternal fructose-fed male offspring.

BACKGROUND AND AIMS: Consumption of food and drinks containing high fructose (HF), which is associated with hypertension, is increasing steeply. Moreover, increased salt intake significantly increases hypertension risk. We examined whether maternal HF and postnatal high salt (HS) intake had synergistic effects on blood pressure (BP) elevation in adult offspring and determined the underlying mechanisms. METHODS AND RESULTS: Pregnant Sprague-Dawley rats received regular chow or chow supplemented with 60% fructose during the entire pregnancy and lactation periods. Half of the male offspring received 1% NaCl in drinking water from weaning to 3 months of age. Male offspring were assigned to 4 groups (control, HF, HS, and HF + HS) and were sacrificed at 12 weeks of age. Offspring in HF and HS groups developed hypertension, indicating that HF and HS synergistically increased BP. Postnatal HS intake increased Ace expression and decreased Agtr1b and Mas1 expression in the kidneys. Renal mRNA levels of Ace and Agtr1a were significantly higher in HF + HS group than in control group. Renal levels of Na-K-2Cl cotransporter, type 3 sodium hydrogen exchanger, and Na(+)/Cl(-) cotransporter were higher in HS and HF + HS groups than in control group. CONCLUSION: Postnatal HS intake exacerbated prenatal HF-induced programmed hypertension. HF and HS induced programmed hypertension by differentially inducing renin-angiotensin system and sodium transporters in the kidneys. Better understanding of the effect of the relationship between HF and HS on hypertension development will help prevent hypertension in mothers and children exposed to HF and HS.

Accelerated resolution of laser-induced bruising with topical 20% arnica: a rater-blinded randomized controlled trial.

BACKGROUND: Dermatological procedures can result in disfiguring bruises that resolve slowly. OBJECTIVES: To assess the comparative utility of topical formulations in hastening the resolution of skin bruising. METHODS: Healthy volunteers, age range 21-65 years, were enrolled for this double (patient and rater) blinded randomized controlled trial. For each subject, four standard bruises of 7 mm diameter each were created on the bilateral upper inner arms, 5 cm apart, two per arm, using a 595-nm pulsed-dye laser (Vbeam; Candela Corp., Wayland, MA, U.S.A.). Randomization was used to assign one topical agent (5% vitamin K, 1% vitamin K and 0·3% retinol, 20% arnica, or white petrolatum) to exactly one bruise per subject, which was then treated under occlusion twice a day for 2 weeks. A dermatologist not involved with subject assignment rated bruises [visual analogue scale, 0 (least)-10 (most)] in standardized photographs immediately after bruise creation and at week 2. RESULTS: There was significant difference in the change in the rater bruising score associated with the four treatments (anova, P=0·016). Pairwise comparisons indicated that the mean improvement associated with 20% arnica was greater than with white petrolatum (P=0·003), and the improvement with arnica was greater than with the mixture of 1% vitamin K and 0·3% retinol (P=0·01). Improvement with arnica was not greater than with 5% vitamin K cream, however. CONCLUSIONS: Topical 20% arnica ointment may be able to reduce bruising more effectively than placebo and more effectively than low-concentration vitamin K formulations, such as 1% vitamin K with 0·3% retinol.

Effects of Cordyceps sinensis on testosterone production in normal mouse Leydig cells.

The stimulatory effect of Cordyceps sinensis (CS) on MA-10 mouse Leydig tumor cell steroidogenesis was previously demonstrated in our laboratory. In the present studies, we further determined the effect of CS on steroidogenesis in purified normal mouse Leydig cells. Different concentrations of CS (0.1-10 mg/ml) were added to Leydig cells without or with human chorionic gonadotropin (hCG) (50 ng/ml), and the steroid production was determined by radioimmunoassay (RIA). The results illustrated that CS stimulated normal mouse Leydig cell steroidogenesis in a dose-dependent relationship. CS at 3 mg/ml significantly stimulated testosterone production (p<0.05). Concerning the temporal relationship, CS at 3 mg/ml stimulated maximal testosterone production between 2 to 3 hr. Interestingly, hCG-stimulated testosterone productions were suppressed by CS in a dose-dependent relationship. CS also reduced dbcAMP-stimulated testosterone productions, which indicated that CS affected signal transduction pathway of steroidogenesis after the formation of cyclic AMP. Moreover, cycloheximide inhibited CS-treated mouse Leydig cell testosterone production, suggesting that new protein synthesis was required for CS-stimulated steroidogenesis.

Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice with an ancient Chinese herb, Ganoderma tsugae.

For centuries, Chinese medicine has regarded Ganoderma, a fungus (Myceteae, Amastigomycota, Busidomycetes, Aphyllophorales, Polyporaceae, Ganoderma) also known as 'Ling Zhi' in Mandarin, as a premium remedy for many diseases. Until now, no convincing data regarding its therapeutic effects in vivo on autoimmune diseases have been demonstrated. In this study, a controlled protocol was conducted in which New Zealand Black/White F1 mice were fed standard chow with prednisolone (0.5 mg/kg/day) or Ganoderma tsugae extract, commencing at 2 months of age. It was found that the F1 mice responded well to Ling Zhi extract. Ling Zhi improved the survival rate of lupus mice, decreased the amount of proteinuria, decreased serum levels of anti-dsDNA autoantibody, and showed evidence of decreased perivascular and parenchyma mononuclear cell infiltration in vital organs.

Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials.

PURPOSE: Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. METHODS AND PATIENTS: One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). RESULTS: Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They consisted of Stage II patients with T2aN0, T1N1, and T2aN1 categories and of Stage III patients with T1N2 and T2aN2 categories. Their risk of recurrence is low (4%). Intermediate-risk patients were those with at least one univariate risk factor. They are Stage II patients with T2bN0 and T2bN1 categories and Stage III patients with T2bN2 and T3N0-2 categories. The risk of recurrence is modest (18%). High-risk patients have risk factors by multivariate analysis. They are stage T4 or N3 patients. Their risk of recurrence is high (36%). CONCLUSION: Low-risk patients have an excellent outcome. Future trials should focus on reducing treatment-associated toxicities and complications and reevaluate the benefit of sequential adjuvant chemotherapy. The recurrence in treatment of intermediate-risk patients is modest; CCRT and adjuvant chemotherapy may be the best standard for them. Patients with T4 and N3 disease have poorer prognosis. Hyperfractionated radiotherapy may be considered for the T4 patients. Future study in these high-risk patients should also address the problem of distant spread of the disease.

Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy.

BACKGROUND: There is increasing evidence that an activation of the immune-inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune-inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune-inflammatory markers in patients with SAD. METHODS: Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy. RESULTS: We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients with SAD than that in normal control controls (P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale-SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy. LIMITATIONS: This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression. CONCLUSIONS: Our results of increased IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune-inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.

Long-term survival of nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy.

PURPOSE: The purpose of this study is to demonstrate long-term survival of nasopharyngeal carcinoma treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy. METHODS AND PATIENTS: One hundred and seven patients with Stage III and IV (American Joint Committee on Cancer, AJCC, 1988) nasopharyngeal carcinoma (NPC) were treated with concomitant chemotherapy and radiotherapy (CCRT) followed by adjuvant chemotherapy between April 1990 and December 1997 in Koo Foundation Sun Yat-Sen Cancer Center, Taipei. The dose of radiation was 70 Gray (Gy) given in 35 fractions, 5 fractions per week. Two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil, were delivered simultaneously with radiotherapy in Weeks 1 and 6 and two additional monthly courses were given after radiotherapy. According to the AJCC 1997 staging system, 32 patients had Stage II disease, 44 had Stage III, and 31 had Stage IV disease. RESULTS: With median follow-up of 44 months, the 5-year overall survival rate in all 107 patients was 84.1%, disease-free survival rate was 74.4%, and locoregional control rate was 89.8%. The 3-year overall survival for Stage II was 100%, for Stage III it was 92.8%, and for Stage IV, 69. 4% (p = 0.0002). The 3-year disease-free survival for Stage II was 96.9%, for Stage III it was 87.7%, and for Stage IV it was 51.9% (p = 0.0001). CONCLUSION: CCRT and adjuvant chemotherapy is effective in Taiwanese patients with advanced NPC. The prognosis of AJCC 1997 Stage II and III disease is excellent, but, for Stage IV (M0), it is relatively poor. Future strategies of therapy should focus on high-risk AJCC 1997 Stage IV (M0) cohort.

Effects of extracted Cordyceps sinensis on steroidogenesis in MA-10 mouse Leydig tumor cells.

Extracts from the mycelium of Cordyceps sinensis (CS) were tested to determine the in vitro effect on Leydig cell function. MA-10 mouse Leydig tumor cells were used to conduct the experiments. Results showed that progesterone production gradually increased as the dosage of combined water and ethanol extracted CS increased, and there was a statistically significant difference in progesterone production stimulated by 20 mg/ml of CS extracts compared to the control. The combined water and ethanol extracted CS significantly stimulated MA-10 cell steroid production at 12 and 24 h of incubation. In addition, a protein synthesis inhibitor, cycloheximide, did not block the stimulatory effects of CS extracts on MA-10 cell steroid production or total protein expression. Moreover, the expression of steroidogenic acute regulatory (StAR) protein, which is a critical protein for steroidogenesis, stimulated by CS extracts, could not be detected by Western blot analysis. These data indicate that CS extracts might not induce StAR protein and/or other protein expressions to stimulate steroidogenesis in MA-10 mouse Leydig tumor cells.

The isolation and structural elucidation of three new neolignans, piperulins [corrected] A, B, and C, as platelet activating factor receptor antagonists from Piper puberulum.

Three new neolignans, piperulins [corrected] A [1], B [2], and C [3], were isolated from Piper puberulum. Their structures and relative stereochemistries were determined from spectral data and the X-ray crystallographic analysis of 1. Compounds 1 and 3 inhibit specific platelet activating factor receptor binding with IC50 values of 7.3 and 5.7 microM, respectively.

Effects of ginseng on the blood chemistry profile of dexamethasone-treated male rats.

Ginseng, a panacea in the Orient, has been widely investigated in the last two decades and found to possess a wide range of pharmacological activities including anti-fatigue properties, a transient regulatory action on metabolism and blood pressure, and an increase in the hypothalamo-pituitary-adrenocortical activities. However, a panoramic clinical chemistry study including adrenal and thyroid functions has never been done before. Two experiments with the same design but different concentrations of dexamethasone were performed in this study. The results obtained from the two experiments indicated that ginseng administration at this regime did not influence the blood chemistry profiles in normal rats, but significantly decreased AST and ALT levels from those in dexamethasone-treated ones. It implies that ginseng has a liver-protective effect. Meanwhile, ginseng therapy restores the adrenal and thyroid functions of rats inhibited by dexamethasone treatment.

[Two-phase test of fecal occult blood screening for colorectal cancer].

The detection of colorectal cancer in an early curable stage has become the focus of considerable interest recently. A two-phase test using both guaiac test and Hemolex latex immuno-agglutination test was applied for fecal occult blood screening of colorectal cancer. A total of 4,725 veterans aging 60 to 69 years were registered, and 2,176 persons (average age 66 years) completed the test giving a compliance rate of 46%. The positive rates of both tests were accounted 20.5% and 6.7% respectively. Five hundred and forty five persons had positive reaction for at least one of the tests. Of these, 90 had a follow up diagnosis with colonoscopy or combined with barium enema. Three rectal adenocarcinomas were detected, of which only one was positive by guaiac test, but two by Hemolex test. A rectal carcinoid was found by rectodigital examination. It was negative by both tests. Nineteen cases were detected to have one or more polyps in colon or rectum, of which only 6 were positive by guaiac test, but 18 by Hemolex test. Hemolex test using antibody against human hemoglobin is based on latex agglutination reaction. It is more sensitive and specific than guaiac test. Moreover, no dietary restriction is required. In the view point of cost-effectiveness, mass screening for colorectal cancer in general public is not recommended, but hospital-based screening for high risk group is still worthwhile to study.

Reconstruction of anorectal angle after abdominoperineal resection of rectum and anus--an animal model.

Voluntary control of the bowel movements is a social necessity. Lack of control relegates one to psychological debility and the possible need for a permanent colostomy. Anorectal angle plays an important role in fecal continence. In the normal individual, this angle lies in the range of 60 to 105 degrees. Perineal colostomy, once proposed for patients who had received abdominoperineal resection (APR), has been abandoned because of frank incontinence. This study used a canine model. The anorectal angle, external sphincter, internal sphincter, and the puborectalis were all destroyed after APR. The colon was pulled through the perineal defect. Enteropexy, gracilis muscle transfer, and perineal colostomy were performed to restore the anorectal angle. Barium enema was performed preoperatively and postoperatively. The anorectal angle was reconstructed within normal ranges after abdominoperineal resection of the rectum and anus.

[Multiple intestinal hemangioma: report of two cases].

Hemangioma of the small intestine is a rare disease which is sometimes very difficult to diagnose because of its anatomical location. This report concerns two cases of multiple intestinal hemangiomas treated surgically. The first case was a four-year-old boy who suffered from recurrent abdominal pain and progressive hemorrhage from the gastrointestinal tract for four months. The character of his abdominal pain was non-specific. On physical examination, whole abdominal tenderness was evident. Serial laboratory and radiological examinations, including abdominal sonogram, barium enema, Tc-99m pertechnetate scan, upper gastrointestinal series failed to reveal abnormality. Multiple intestinal hemangiomas were found at exploratory laparotomy. The second case was a new-born suffering from fetal ascites. Abdominal sonogram, barium enema, voiding cystourethrography were performed without significant findings, and the diagnose of multiple intestinal hemangiomas was proved by laparotomy. In both, symptoms improved after segmental resection of the bowels. The purpose of this paper is to draw attention to the possibility of intestinal hemangioma as a source of recurrent abdominal pain, tarry stool or ascites in children.

Evaluation of rapid colon preparation with Golytely.

The traditional cleansing method of the large bowel usually involves dietary restrictions, purgatives and enema. They are time consuming and uncomfortable, and may result in dehydration. Though Golytely, an oral lavage solution, has been developed since 1980 as an alternative for cleansing the colon and much literature has favored it, it has not been widely used in Taiwan. In this study, we used Golytely without enema for rapid colon cleansing in a consecutive series of 48 patients. The efficacy, change of vital signs, body weights, electrolytes, and urine specific gravity were evaluated. Patient's acceptance of this method was compared with that of 32 patients who received castor oil as cleansing method. The average amount of Golytely used in this preparation was 3.16 liters, and the average time was 8 hours and 43 minutes. About 87% of patients receiving Golytely achieved a good to excellent preparation. There were no significant changes in vital signs, body weights, electrolytes and urine specific gravity. The patient's acceptance of Golytely was better than that of castor oil.

Alterations in physiologic functions and in brain monoamine content in streptozocin-diabetic rats.

In the present study, we used streptozocin (STZ) to induce diabetes in rats and observed alterations in several physiologic functions and in monoamine content of different brain regions. Rats with STZ diabetes displayed a thermoregulatory deficit in the cold. Both the body temperature and metabolic rate of the diabetic animals were reduced at ambient temperatures below 22 degrees C. These diabetic animals had a higher level of the spontaneous pain threshold, but displayed a reduced sensitivity of analgesic responses to morphine injection. In addition, these diabetic animals had a lower level of spontaneous motor activity, but displayed an increased sensitivity of locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that the diabetic animals had a lower serotonin level in both the hypothalamus and the brainstem without changes in the serotonin levels of the corpus striatum. These diabetic animals also had a lower catecholamine level in the hypothalamus, but a higher catecholamine level in the corpus striatum. The alterations in brain monoamine content and in the above-mentioned physiologic parameters were reversed after insulin replacement therapy. The data suggest that alterations in various autonomic, somatosensory, and motor neural functions of untreated STZ-diabetic rats correlated with a reproducible pattern of monoamine content in various brain regions (a pattern that differed from that observed in healthy control rats), and that both the altered neural function and the altered brain monoamine pattern were reversed after insulin therapy.

Clonidine-induced hypothermia: possible involvement of cholinergic and serotonergic mechanisms.

The thermoregulatory effects (including metabolic, vasomotor and respiratory activities) produced by an injection of clonidine (1-3 micrograms in 0.5 microliter) into the preoptic anterior hypothalamus were assessed in conscious rats at ambient temperatures (Ta) of 8, 22 and 30 degrees C. Intrahypothalamic administration of clonidine caused a dose-dependent fall in rectal temperature at Ta 8 degrees C and 22 degrees C. The hypothermia in response to clonidine was due to decreased metabolic heat production and/or cutaneous vasodilation. There was no change in respiratory evaporative heat loss. The clonidine-induced hypothermic response was attenuated by pretreatment of the rats with either 5,7-dihydroxytryptamine (10 micrograms, administered intrahypothalamicly, 14 days before clonidine injection), yohimbine (0.2 microgram, administered intrahypothalamicly, 10 min before clonidine injection), cyproheptadine (1 microgram, administered intrahypothalamicly, 10 min before clonidine injection), or atropine (0.1 microgram, administered intrahypothalamicly, 10 min before clonidine injection). The data indicate that clonidine may act on alpha-adrenoceptors located on a serotonin-acetylcholine pathway within the preoptic anterior hypothalamus to induce hypothermia by promoting a reduction in metabolic heat production and/or an enhancement in dry heat loss in rats.

Effects of hypothalamic noradrenaline depletion with 6-hydroxydopamine on the body temperature regulation of the rat.

Rats which had been pretreated with 3 intrahypothalamic doses of 10 micrograms of 6-hydroxydopamine (6-OHDA) to cause a selective depletion of hypothalamic noradrenaline to 26.7% of control hypothalamic noradrenaline maintained rectal temperature within the normal limits displayed by the control group. However, noradrenaline-depleted rats displayed a decrease in both cutaneous temperature and metabolic heat production in the cold (8 degrees C). Intrahypothalamic injections of 6-OHDA in normal rats at room temperature (22 degrees C) caused an acute hyperthermia of up to 1.1 degree C which lasted for about 6 h. The acute hyperthermia in response to 6-OHDA was due to both cutaneous vasoconstriction and increased metabolism in the rat. Selective depletion of hypothalamic noradrenaline without affecting hypothalamic dopamine by prior treatment with 6-OHDA markedly reduced the hyperthermic responses to a subsequent dose of 6-OHDA. Therefore, the acute hyperthermic responses to 6-OHDA may be related to a release of noradrenaline in the hypothalamus. The data indicate that activation of noradrenergic pathways in the hypothalamus facilities heat production and inhibits heat loss mechanisms in the rat.