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PubMed2006

Estrogenic control of thermoregulation in ERalphaKO and ERbetaKO mice.

OBJECTIVE: Estrogen is the most effective treatment for preventing the vasomotor symptoms in women. The ability of estrogen to control tail skin temperature (TST) in rats is used as an animal model for the studies of estrogens on menopausal hot flushes. Today, we know that estrogen can mediate its actions via the interaction with two different estrogen receptors: ERalpha and ERbeta. To elucidate the function of each estrogen receptor subtype control of thermoregulation, we developed an animal model demonstrating estrogen control of TST in mice. METHODS AND RESULTS: We determined that estrogen depletion by ovariectomy (OVX) of mice causes an elevation of basal tail skin temperature. Administration of estradiol cypionate suppressed this increase in TST in a dose dependent manner. Estrogen depletion by OVX in either ERalpha-knockout (ERalphaKO) or ERbeta-knockout (ERbetaKO) mice resulted in an increase in TST that could be suppressed by estrogen treatment. CONCLUSION: We show that mice serve as a suitable animal model for estrogen-controlled thermoregulation and that the expression of either ERalpha or ERbeta alone in mice is sufficient to maintain control TST by estrogen.

Animals↗
PubMedDate not supplied

[The clinico-pharmacological characteristics of anteovin].

The clinical and laboratory studies carried out on 160 women showed a high contraceptive effect and good tolerance of anteovine. The contraceptive effect of the biphasic drug is determined by its antiovulatory action concurrent with inhibition of the basal periovulatory secretion of gonadotropins and secretion of sex hormones.

Adolescent↗
PubMed1997

CL-316,243, a beta3-specific adrenoceptor agonist, enhances insulin-stimulated glucose disposal in nonobese rats.

Administration of the murine-selective beta3 adrenoceptor agonist CL-316,243 corrects obesity and elevated blood glucose in diabetic rodents. This antiobesity effect is attributed to an increase in the thermogenic activity of brown adipose tissue (BAT). The antidiabetic effect is unknown, but has been attributed to the decline in body weight and plasma free fatty acids (FFAs). This study using the euglycemic-hyperinsulinemic clamp method was performed in nonobese, nondiabetic Sprague-Dawley rats fed normal rodent chow to determine if the beta3 agonist could improve insulin sensitivity and/or responsiveness in the absence of weight loss or lowering of circulating FFAs. Subcutaneous miniosmotic pumps delivered either saline to control or 1 mg x kg(-1) x day(-1) of CL-316,243 for 10-12 days. Fed plasma glucose, insulin, and FFA levels were similar between the groups. Significant increases in food consumption, resting metabolic rates, and body core temperatures occurred, but only after 7 days of treatment. A 14% decrease in the respiratory quotient was also observed. Plasma glucose and insulin excursions in response to an oral glucose load (2 g/kg) on day 11 were unaltered. Cl-316,243 treatment resulted in a decrease in abdominal and epididymal white fat pad weights, while interscapular brown adipose tissue (IBAT) weight doubled. Basal and insulin-stimulated whole-body glucose disposal rates were increased, while hepatic glucose output was suppressed to a greater extent in the CL-316,243 animals after 10 days of uninterrupted treatment. Chronic treatment with CL-316,243 resulted in an increase in basal and insulin-stimulated [3H]2-deoxyglucose (2-DG) uptake by the retroperitoneal and epididymal white tissue and IBAT, but skeletal muscle 2-DG uptake under the same conditions was unaltered. These studies demonstrate that treatment with CL-316,243 improves basal and insulin-stimulated glucose disposal, and these effects occurred in the absence of a decrease in body weights and FFA concentrations. A particularly interesting observation was that the tissues responsible for this effect were white and brown adipose tissue, while skeletal muscle remained unaffected.

Adipose Tissue↗
PubMed1993

Fine structure of zonal changes in experimental Nd:YAG laser-induced interstitial hyperthermia.

Interstitial thermotherapy using Nd:YAG-laser induced hyperthermia is a new stereotactic method for the treatment of brain tumors in poorly accessible regions. To provide a basis for the underlying tissue alterations, we have analyzed the spatial and temporal pattern of interstitial laser hyperthermia lesions in the normal rat brain by histological, immunohistochemical, and electron microscopical methods. The acute changes corresponded to the temperature gradient surrounding the laser probe and showed a distinct zonal architecture. Membrane destruction on a cellular and subcellular level appears to be of major significance in the pathogenesis of the laser lesion. The tissue reaction followed the course known for coagulation necrosis and resulted in a well-defined defect. These results, although limited by the choice of the experimental model, may be helpful in the interpretation of images obtained in future applications of interstitial thermotherapy.

Aluminum Silicates↗
PubMed2006

Human skin preserved long-term in anhydric pulverized sodium chloride retains cell molecular structure and resumes function after transplantation.

BACKGROUND: Human skin is needed to cover large areas of the body lost through burns, trauma, and extensive maxillofacial surgery. Contemporary methods of skin storage are limited by the period of preservation to a few days. Our previous findings showed that fixation and storage of human skin in anhydric sodium chloride at room temperature for weeks or months preserves its morphological and molecular structure. In this study, we examined whether skin grafts preserved in sodium chloride may be successfully transplanted. METHODS: Skin was harvested from lower limbs of patients during elective surgery, placed in containers with anhydric salt powder, and kept at 22 degrees C for 3 to 12 weeks. Desalination and rehydration took place before transplantation. Desalinated fragments were transplanted onto the dorsum of scid mice. RESULTS: All grafts were accepted by recipients. Three weeks after transplantation, keratinocytes synthesized keratins 10, 16, and 17 and expressed antigens specific for stem (p63) and transient (CD29) cells. Moreover, they proliferated vigorously, their basal layer cells incorporated bromdeoxyuridine and expressed proliferative cell nuclear antigen. Isolated from transplants and cultured in vitro, they remained viable and produced enzymes. Dermis retained its structure and expressed fibroblast-specific antigen. All graft cells remained human leukocyte antigen I. CONCLUSION: Human skin preserved in anhydric sodium chloride at room temperature for months can be successfully transplanted to scid mice. We propose the concept of "spore-like" keratinocyte stem cells to explain the long-term ex vivo survival of keratinocytes. The mechanism of survival of fibroblasts remains to be determined.

Animals↗
PubMed2003

Assessment of resting energy expenditure in mechanically ventilated patients.

BACKGROUND: Usual equations for predicting resting energy expenditure (REE) are not appropriate for critically ill patients, and indirect calorimetry criteria render its routine use difficult. OBJECTIVE: Variables that might influence the REE of mechanically ventilated patients were evaluated to establish a predictive relation between these variables and REE. DESIGN: The REE of 70 metabolically stable, mechanically ventilated patients was prospectively measured by indirect calorimetry and calculated with the use of standard predictive models (Harris and Benedict's equations corrected for hypermetabolism factors). Patient data that might influence REE were assessed, and multivariate analysis was conducted to determine the relations between measured REE and these data. Measured and calculated REE were compared by using the Bland-Altman method. RESULTS: Multivariate analysis retained 4 independent variables defining REE: body weight (r(2) = 0.14, P < 0.0001), height (r(2) = 0.11, P = 0.0002), minute ventilation (r(2) = 0.04, P = 0.01), and body temperature (r(2) = 0.07, P = 0.002): REE (kcal/d) = 8 x body weight + 14 x height + 32 x minute ventilation + 94 x body temperature - 4834. REE calculated with this equation was well correlated with measured REE (r(2) = 0.61, P < 0.0001). Bland-Altman plots showed a mean bias approaching zero, and the limits of agreement between measured and predicted REE were clinically acceptable. CONCLUSION: Our results suggest that REE estimated on the basis of body weight, height, minute ventilation, and body temperature is clinically more relevant than are the usual predictive equations for metabolically stable, mechanically ventilated patients.

Basal Metabolism↗
PubMedDate not supplied

Correlation between measured energy expenditure and clinically obtained variables in trauma and sepsis patients.

BACKGROUND: Indirect calorimetry is the preferred method for determining caloric requirements of patients, but availability of the device is limited by high cost. A study was therefore conducted to determine whether clinically obtainable variables could be used to predict metabolic rate. METHODS: Patients with severe trauma or sepsis who required mechanical ventilation were measured by an open-circuit indirect calorimeter. Several clinical variables were obtained simultaneously. Measurements were repeated every 12 hours for up to 10 days. RESULTS: Twenty-six trauma and 30 sepsis patients were measured 423 times. Mean resting energy expenditure was 36 +/- 7 kcal/kg (trauma) vs 45 +/- 8 kcal/kg (sepsis) (p < .0001). The single strongest correlate with resting energy expenditure was minute ventilation (R2 = 0.61, p < .0001). Doses of dopamine, dobutamine, morphine, fentanyl, and neuromuscular blocking agents each correlated positively with resting energy expenditure. In the case of the inotropics and neuromuscular blockers, there was a probable covariance with severity of illness. A multiple regression equation was developed using minute ventilation, predicted basal energy expenditure, and the presence or absence of sepsis: resting energy expenditure = -11000 + minute ventilation (100) + basal energy expenditure (1.5) + dobutamine dose (40) + body temperature (250) + diagnosis of sepsis (300) (R2 = 0.77, p < .0001). CONCLUSION: Severe trauma and sepsis patients are hypermetabolic, but energy expenditure is predictable from clinical data. The regression equations probably apply only to severe trauma and sepsis. Other studies should be conducted to predict energy expenditure in other patient types.

Adult↗
PubMed2003

Thermal response to submaximal exercise before, during and after pregnancy: a longitudinal study.

BACKGROUND: Heat stress in early pregnancy is known to have a teratogenic effect. Exercise produces excess heat and during pregnancy might therefore present a theoretical risk of malformations. Our aim was to assess the thermal response to exercise of healthy pregnant women in a longitudinal study. METHODS: Fourteen women were examined before pregnancy, and followed five times during, and twice after pregnancy, using a submaximal bicycle test with a target heart rate of 85% of the predicted age-adjusted maximum. The main aim was to present reference values. RESULTS: The temperature at submaximal work load declined continuously from preconception to postpartum levels (37.8 degrees C vs. 36.9 degrees C, p = 0.04). The difference between peak and basal core temperature fell from 0.6 degrees C to 0.05 degrees C at 29 and 36 weeks of gestation, reaching preconception levels at 24 weeks after delivery (0.8 degrees C lower). CONCLUSION: During submaximal exercise the temperature response seemed to provide thermal protection for the embryo and the fetus.

Adult↗
PubMed1995

Cold water immersion simulations using the Wissler Texas Thermal Model: validation and sensitivity analysis.

BACKGROUND: Wissler's Texas Thermal Model (TM) has been used to simulate the effects of thermal stresses on individuals under a variety of conditions. As part of a U.S. Navy effort to develop integrated protection garments, TM was modified to predict tolerance to cold water immersion (CWI) with garments with clo values less than 0.1 (15). METHODS: With these modifications, TM predictions were validated using experimental data obtained from 39 males and females during anti-exposure suit CWI assessments. Data analyses were based on changes in rectal (Tre) and various skin temperatures (Tsk). A sensitivity analysis was also performed to determine which TM parameters were most affected during simulated CWI. The condition tested was head-out immersion in 4.4 degrees C water by a 72.6 kg man (10 mm mean skinfold thickness). RESULTS: For most of the subject pool, the estimated change in Tre, chest, thigh, calf, and arm temperatures were not statistically different from experimental values. However, TM predictions were less accurate with respect to female responses. Based on thermal end points, TM predictions indicated that the following body segments were most sensitive to changes in insulation level (ordered from most to least important): chest and abdomen, leg, head, and arm. The physical parameters mean skinfold thickness, basal metabolic rate, body weight, and exercise metabolic rate had the most impact on TM predictions. CONCLUSIONS: The relative benefit of increased insulation on individual body segments was identified to aid garment design. Further, the relative importance of model physical parameters was identified so that judicious initial conditions could be selected to ensure that only garment design changes would be reflected in model predictions.

Abdomen↗
PubMed1985

[Clinical long term observations on the function of ovaries autotransplanted at radical hysterectomy on cervical carcinoma patients].

A policy to preserve the ovary is adopted in our seminar when subjects are young women and the type of the tissue is squamous cell carcinoma during total radical hysterectomy of cervical carcinoma. As one of the preservation methods, by pathohistological examination for operatively extirpated matter, postoperative radiation therapy is indicated to the cases a) that infiltration into the parametrium is observed, b) that residue of infiltrate tissue is guessed in a segment of the vagina and c) that metastasis to the pelvic lymph node is confirmed. However, during practice of postoperative irradiation, ovarian autotransplantation to outside of irradiating field has been carried out to prevent functional extinction of preserved ovary due to irradiation. As transplantation, the ovary is detached from the peripheral tissue with connecting the ovarian artery and vein to it to make movable, then is moved and transplanted with both vessels. There are two sites for transplantation, which are the submamma and the upper lateral region of abdomen. Thus subcutaneous preservation is done in a manner of envelopment with lipid. Most ovaries transplanted begin to repeat swelling and reduction according to ovulocycle. Patients record change in ovarian size concurrently with basal body temperature (BBT). In addition, we have been continuing measurement of LH, FSH, estradiol and progesterone in the blood to examine endocrine function of transplanted ovary during regular physical examination over a long period for discharged patients. In this study, out of 61 cases with transplantation, especially, 43 cases for whom long term follow-up for 6 years since 6 months after transplantation had been able to be carried out were researched about their ovarian functions. We report on it together with existence of influence of preserved ovary to therapeutic findings in cervical carcinoma. All of 43 cases show continuation of ovarian swelling cycle. In 28 cases recording both BBT and ovarian swelling, analysis for total of 407 cycles revealed normal biphasic cycle, 54.8%, luteal phase insufficient cycle, 23.1% and luteal phase defect cycle, 11.3%. Analysis of blood hormones in 26 cases showed the same secretory activity of sex hormones in each cycle of transplanted ovaries as that in normal mature ovaries, and showed maintenance of feed back to sex center.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMedDate not supplied

Evaluation of nitric oxide synthesis in the optic nerve head in vivo using microdialysis and high-performance liquid chromatography and its interaction with endothelin-1.

PURPOSE: To investigate the relationship between nitric oxide synthesis and endothelin-1 (ET-1) in the optic nerve head in vivo. METHODS: A concentric microdialysis probe was inserted into the optic nerve head of a rabbit and was perfused with Ringer's solution at a constant flow rate of 2 microl/min. The perfused dialysates were collected every 10 min, and levels of nitrite and nitrate in the 10-min dialysate samples were measured after intravitreal injection of ET-1 (100 pmol) using high-performance liquid chromatography based on the Griess method. RESULTS: Basal levels of nitrite and nitrate in the 10-min dialysate were 0.08 +/- 0.01 and 3.95 +/- 0.50 microM, respectively. We confirmed that these levels were reduced by intravenous L-NAME and restored by L-arginine. Intravitreal ET-1 significantly elevated the levels of nitrate to 189% of baseline 10 min after ET-1 application, which was inhibited by pretreatment of intravenous L-NAME (50 mg/kg). CONCLUSION: These results indicate that production of nitric oxide is closely connected with the ET-1 signaling pathway.

Analysis of Variance↗
PubMed1993

Effect of the pattern of food intake on human energy metabolism.

The pattern of food intake can affect the regulation of body weight and lipogenesis. We studied the effect of meal frequency on human energy expenditure (EE) and its components. During 1 week ten male adults (age 25-61 years, body mass index 20.7-30.4 kg/m2) were fed to energy balance at two meals/d (gorging pattern) and during another week at seven meals/d (nibbling pattern). For the first 6 d of each week the food was provided at home, followed by a 36 h stay in a respiration chamber. O2 consumption and CO2 production (and hence EE) were calculated over 24 h. EE in free-living conditions was measured over the 2 weeks with doubly-labelled water (average daily metabolic rate, ADMR). The three major components of ADMR are basal metabolic rate (BMR), diet-induced thermogenesis (DIT) and EE for physical activity (ACT). There was no significant effect of meal frequency on 24 h EE or ADMR. Furthermore, BMR and ACT did not differ between the two patterns. DIT was significantly elevated in the gorging pattern, but this effect was neutralized by correction for the relevant time interval. With the method used for determination of DIT no significant effect of meal frequency on the contribution of DIT to ADMR could be demonstrated.

Adult↗
PubMed1988

The use of anti-progesterones as a medical IUD.

Mifepristone holds promise as a safe and effective anti-progesterone. Widespread use of mifepristone to regularize cycles or prevent pregnancy, however, cannot be recommended at this time. The drug is promising for these uses but the dose and timing of administration required to achieve optimum effect are unknown. Menses are consistently induced in the mid to late luteal phase at a wide range of doses. Further work needs to be done to examine the luteolytic properties of the drug when given at this time. Knowledge about the serum concentration of the parent compound and its less active metabolites after oral administration may help to explain variable biological effects. The effects of other modes of administration, such as transdermal or transvaginal application which avoid a first-pass effect by the liver, should also be explored. Practical issues of the timing of administration need to be resolved. The drug is not effective when given in the absence of luteal phase levels of progesterone. Thus, verification of luteal phase status before the administration of the drug would be ideal. Basal body temperature monitoring may be one way to do this. There is no other convenient way to determine serum levels of progesterone that would be feasible on a large-scale outpatient basis. Since mifepristone does not regulate the timing of ovulation, the optimal time of administration may vary from cycle to cycle. This presumes a high degree of willingness on the part of the woman to observe her cycles and participate in decisions regarding the timing of the drug. Mifepristone, the first clinically available anti-progesterone, represents a significant advance in fertility control.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMedDate not supplied

Effect of neuromuscular blockade on energy expenditure in patients with severe head injury.

BACKGROUND: The purpose of this study was to determine the effect of neuromuscular blockade on energy expenditure in severely head-injured patients; to determine the effects of body temperature, nutrition support, and morphine use on metabolic rate; and to compare measured energy expenditure with values from predictive equations. METHODS: Energy expenditure was measured using indirect calorimetry in 2 groups of ventilated patients-18 with severe head injury during and after administration of pancuronium bromide and morphine, and second, 14 severely traumatized patients without severe head injury (trauma group) who received morphine without neuromuscular blockade. RESULTS: The mean energy expenditure of head-injured patients increased significantly once pancuronium was discontinued, ie, from 24.2 +/- 3.1 to 28.7 +/- 4.6 kcal/kg (p = .002). This effect was independent of other relevant variables such as morphine dose, body temperature, and nutrition support. When compared with the Harris-Benedict and World Health Organization predictive equations, neuromuscular blockade resulted in a stress factor of only 0.96 and 0.95, respectively, which increased to 1.19 and 1.18, respectively, once blockade was discontinued. Head-injured patients not on neuromuscular blockade had a significantly greater energy expenditure when compared with the trauma group (p = .02). CONCLUSIONS: Neuromuscular blockade in severely head-injured patients decreases energy expenditure to basal levels, independent of morphine use, body temperature, and feeding. Levels of hypermetabolism in both the head-injured and trauma groups were relatively low, at 19% and 5% above predicted values, respectively. This study provides useful information for the management of nutrition support in severely traumatized patients.

Adolescent↗
PubMed2000

Nitric oxide and thermogenic function of brown adipose tissue in rats.

To clarify the effects of cold acclimation and immobilization stress adaptation of rats on nitric oxide (NO) activity in interscapular brown adipose tissue (BAT), we incubated neatly diced (1-mm(3) blocks) BAT in a metabolic chamber for respiration, measured oxygen consumption using a Clark electrode, and estimated NO release in the buffer medium by measuring nitrite plus nitrate (NO(x)) using the Griess method (diazotization reaction). The production of NO(x) in the buffer medium confirmed that BAT releases NO, as there is no other source of NO(x) in the system. The NO activity was observed in the basal condition and increased with noradrenaline stimulation, showing a correlation with oxygen consumption in the warm (25 degrees C)-acclimated control rats. Cold acclimation (5 degrees C, 5 weeks) or immobilization stress adaptation (3 h daily, 25 degrees C, 5 weeks) caused enhanced NO activity in the basal condition in comparison with the control. We suggest that NO is involved in enhancement of the thermogenic functions of BAT in rats.

Acclimatization↗
PubMedDate not supplied

Attributes of the oral cavity as a site for basal body temperature measurements.

The thermal topography of the oral cavity of 11 women was mapped with thermocouples in early morning waking conditions. A reference thermocouple was placed in the vagina. No significant difference was found in the time required to reach a steady-state oral temperature and in the achieved steady-state temperature difference (Tv-To) in the preovulatory and postovulatory phases of the menstrual cycle. Location of the thermocouple in the oral cavity had a significant effect on steady-state temperature differences. After equilibration of oral thermometers, women breathed through their mouths for exactly five minutes. Mouths were closed and a second temperature equilibration phase was recorded. Mouth breathing had a significantly greater effect on the temperature of the anterior sublingual and dorsum of the tongue sites than on the posterior sublingual and buccal trough sites.

Adult↗
PubMed2004

A nutritional supplement for improving fertility in women: a pilot study.

OBJECTIVE: To determine the impact of nutritional supplementation on optimization of reproductive health in women. STUDY DESIGN: A double-blind, placebo-controlled pilot study was initiated to determine the effects of FertilityBlend (Daily Wellness Co., Sunnyvale, California), a proprietary nutritional supplement containing chasteberry and green tea extracts, L-arginine, vitamins (including folate) and minerals. Changes in progesterone level, basal body temperature, menstrual cycle, pregnancy rate and side effects were monitored. RESULTS: Thirty women aged 24-46 years who had tried unsuccessfully to conceive for 6-36 months completed the study. After 3 months, the supplement group (n = 15) demonstrated a trend toward an increase in mean midluteal phase progesterone level (from 8.2 to 12.8 ng/mL, P = .08) and a significant increase in the average number of days in the cycle with basal temperatures >37 degrees C during the luteal phase (6.8-9.7 days, P = .04). The placebo group (n = 15) did not show any notable changes after treatment in any of the parameters studied. After 5 months, 5 of the 15 women in the supplement group were pregnant (33%), and none of the 15 women in the placebo group were (P <.01). No significant side effects were noted. CONCLUSION: Nutritional supplementation may provide an attractive alternative or complement to conventional fertility therapy.

Adult↗
PubMed2002

Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary Raynaud's phenomenon: effect of cold exposure.

OBJECTIVE: F2-isoprostanes are free radical-dependent arachidonic acid metabolites that are used as clinical markers of lipid peroxidation in systemic sclerosis (SSc) and other microvascular diseases. The objectives of this study were to determine whether the basal urinary levels of F2-isoprostane in SSc patients differ from those in patients with primary Raynaud's phenomenon (RP) and to investigate whether F2-isoprostane formation correlates with the cutaneous microvascular perfusion decrease following cold exposure in SSc patients, patients with primary RP, and healthy controls. METHODS: Eleven women with RP secondary to SSc, 11 women with primary RP, and 11 healthy women were exposed to decreasing room temperature, from 25 degrees C to 15 degrees C, for 40 minutes. Urine samples were obtained before and after the test for gas chromatography/electronic impact mass spectrometry quantification of 15-F(2t)-isoprostane (15-F(2t)-IsoP; also called isoprostaglandin F(2alpha) type III). Cutaneous blood flow was monitored using a laser Doppler perfusion imager. RESULTS: The mean +/- SEM urinary 15-F(2t)-IsoP levels at baseline in SSc patients (178 +/- 32 pmoles/mmole of creatinine) were 1.9 times higher than those in healthy controls (95 +/- 11 pmoles/mmole of creatinine) and 1.7 times higher than those in patients with primary RP (107 +/- 19 pmoles/mmole of creatinine) (P < 0.05 for controls and patients with primary RP versus SSc patients). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and the temperature or cutaneous blood flow decrease in response to the whole-body cooling. Furthermore, the 15-F(2t)-IsoP response to the cooling test was not correlated with the cutaneous blood flow decrease. CONCLUSION: Lipid peroxidation is increased in SSc patients, but not in patients with primary RP. Cold exposure leads to a significant but small increase in 15-F(2t)-IsoP levels that is independent of the cutaneous blood flow decrease. F2-isoprostane quantification may be an interesting pharmacologic tool for monitoring responses to antioxidant treatment in SSc patients.

Adult↗