Short-Term Outcomes of Conventional Laparoscopic versus Robot-Assisted Distal Pancreatectomy for Malignancy: Evidence from US National Inpatient Sample, 2005-2018.

BACKGROUND: The primary treatment for pancreatic cancer is surgical resection, and laparoscopic resection offers benefits over open surgery. This study aimed to compare the short-term outcomes of robot-assisted vs. conventional laparoscopic distal pancreatectomy. METHODS: Data of adults ≥ 20 years old with pancreatic cancer who underwent conventional laparoscopic or robot-assisted laparoscopic distal pancreatectomy were extracted from the United States (US) Nationwide Inpatient Sample (NIS) 2005-2018 database. Comorbidities and complications were identified through the International Classification of Diseases (ICD) codes. Short-term outcomes were compared using logistic regression and included length of hospital stay (LOS), perioperative complications, in-hospital mortality, unfavorable discharge, and total hospital costs. RESULTS: A total of 886 patients were included; 27% received robot-assisted, and 73% received conventional laparoscopic surgery. The mean age of all patients was 65.3 years, and 52% were females. Multivariable analysis revealed that robot-assisted surgery was associated with a significantly reduced risk of perioperative complications (adjusted odds ratio (aOR) = 0.61, 95% confidence interval (CI): 0.45-0.83) compared to conventional laparoscopic surgery. Specifically, robot-assisted surgery was associated with a significantly decreased risk of VTE (aOR = 0.35, 95% CI: 0.14-0.83) and postoperative blood transfusion (aOR = 0.37, 95% CI: 0.23-0.61). Robot-assisted surgery was associated with a significantly shorter LOS (0.76 days shorter, 95% CI: -1.43--0.09) but greater total hospital costs (18,284 USD greater, 95% CI: 4369.03-32,200.70) than conventional laparoscopic surgery. CONCLUSIONS: Despite the higher costs, robot-assisted distal pancreatectomy is associated with decreased risk of complications and shorter hospital stays than conventional laparoscopic distal pancreatectomy.

Hypothalamic impairment underlying heat intolerance in pregnant mice.

Pregnant women are vulnerable to heat stroke reactions caused by high environmental temperatures. Heat intolerance is associated with hypothalamic impairment. Here, we aim to ascertain whether pregnancy causes heat intolerance by inducing hypothalamic impairment in mice. In the heated groups, mice were exposed to whole body heating (WBH; 41.2 °C for 1 h) in an environment-controlled chamber. Then, they were returned to normal room temperature (26 °C) immediately after WBH. In the hyperbaric oxygen therapy (HBO2T) groups, mice were exposed to 100% O2 at 2.0 atm absolute (ATA) for 4 h immediately post-WBH. Mice that survived after 4 h of WBH were considered survivors. Here, we show that when pregnant mice underwent non-HBO2T (21% O2 at 1.0 ATA for 4 h) after WBH, the survival rate was 4/20, and the core temperature at 4 h post-WBH was 31.2 ±â€¯0.2 °C. Both the survival rate and core temperature of HBO2T pregnant mice (10/10 and 35.2 ±â€¯0.3 °C, respectively) were significantly greater than those in non-HBO2T pregnant mice. Compared to non-HBO2T heated mice, the HBO2T heated mice exhibited lower neurological severity scores, reduced hypothalamic neuronal damage, fewer apoptotic cells, reduced multiorgan damage scores, and lower hypothalamic levels of proinflammatory cytokines and nitrogen and oxygen radical species. Compared to non-HBO2T heated mice, the HBO2T-treated heated mice had significantly higher hypothalamic-pituitary-adrenal axis activity (evidenced by higher serum levels of both adrenocorticotrophic hormone and corticosterone). In conclusion, pregnancy induces heat intolerance by inducing hypothalamic impairment in mice. Additionally, HBO2T protects against heat intolerance in pregnant mice by preserving hypothalamic integrity.

Attenuating spinal cord injury by conditioned medium from human umbilical cord blood-derived CD34⁺ cells in rats.

OBJECTIVE: Intravenous or intraspinal transplantation of human umbilical cord blood cells-derived CD34(+) cells (human CD34(+) cells) or mesenchymal stem cells after spinal cord injury (SCI) improved hind limb functional recovery in adult rats. The objective of this study is to ascertain whether SCI in rats can be attenuated by conditioned medium (CM) or secretome obtained from cultured human CD34(+) stem cells. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: the sham group, the SCI group treated with vehicle solution (SCI + V), the SCI group treated with CM (SCI + CM), the SCI group treated with 17ß-estradiol E2 (10 µg; SCI + E2), and the SCI group treated with CM plus E2 (SCI + CM + E2). A 0.5-mL volume of CM or vehicle solution was administered intravenously immediately after SCI. RESULTS: Compared with the sham group, the (SCI + V) group had significantly higher scores of neurological motor dysfunction as well as inflammation apoptosis, oxidative stress, and astrogliosis in the injured spinal cord. The neurological deficits, numbers of apoptotic cell, extent of inflammation, oxidative stress, and astrogliosis in the injured spinal cord were significantly attenuated by CM, E2, or CM plus E2, but not by the vehicle solution. In addition, the neuroprotective effect exerted by a combination of CM and E2 is superior to that exerted by CM- or E2-alone therapy. CONCLUSION: The neuroprotective effects of CM from cultured human CD34(+) cells are similar to those of human CD34(+) cells and the CM was found to enhance the neuroprotective effects of E2 in rat SCI.

17ß-Estradiol Accelerated Renal Tubule Regeneration in Male Rats After Ischemia/Reperfusion-Induced Acute Kidney Injury.

Ischemic/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI). Murine studies report that pretreatment with 17ß-estradiol protects against AKI using multiple mechanisms, but how 17ß-estradiol is involved in regenerating tubular cells is unknown. To visualize the kidney injury and repair, we used 17ß-estradiol to treat rats with postischemic acute kidney injury. AKI was induced by clamping the renal pedicle for 90 minutes 2 weeks after a unilateral nephrectomy. Rats were treated with an intravenous injection of 17ß-estradiol or vehicle immediately after reperfusion. Kidney injury was assessed by measuring biochemical and histopathological changes. Immunohistochemical staining of vimentin, proliferating cell nuclear antigen (PCNA), and E-cadherin were used to assess dedifferentiation, proliferation, and redifferentiation. Rats treated with 17ß-estradiol had less kidney injury than did vehicle-treated rats post-IRI day 1. The number of PCNA-positive (PCNA) cells was significantly higher in post-IRI kidneys on day 1 in 17ß-estradiol-treated rats. Moreover, vimentin and E-cadherin cells, which were interpreted as regeneration markers, were expressed earlier and significantly more copiously in 17ß-estradiol-treated rats. We hypothesize that 17ß-estradiol attenuates IRI-induced AKI by reducing inflammation and accelerating injured tubular cell regeneration.

The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO). Experiment 2 was to evaluate the adjuvant effect of 17ß-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment) caused less infarction size than those infused after MCAO (post-treatment) on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

Therapeutic treatment with ascorbate rescues mice from heat stroke-induced death by attenuating systemic inflammatory response and hypothalamic neuronal damage.

The impact of ascorbate on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. Heatstroke is defined as a form of excessive hyperthermia associated with a systemic inflammatory response that results in multiple organ dysfunctions in which central nervous system disorders such as delirium, convulsions, and coma are predominant. The thermoregulatory, immune, coagulation and tissue injury responses of heatstroke closely resemble those observed during sepsis and are likely mediated by similar cellular mechanisms. This study was performed by using the characteristic high lethality rate and sepsis-mimic systemic inflammatory response of a murine model of heat stroke to test our hypothesis that supra-physiological doses of ascorbate may have therapeutic use in critical care. We demonstrated that parenteral administration of ascorbate abrogated the lethality and thermoregulatory dysfunction in murine model of heat stroke by attenuating heat stroke-induced accelerated systemic inflammatory, coagulation responses and the resultant multiple organ injury, especially in hypothalamus. Overall, our findings support the hypothesis and notion that supra-physiological doses of ascorbate may have therapeutic use in critical care.

BRCA1 mislocalization associated with breast carcinogenesis and poor prognosis in Taiwanese women.

We aimed to elucidate whether and how BRCA1 mislocalization [including membranous nuclear (MN) forms and negative patterns] is associated with the occurrence and the prognosis of breast cancer in young Taiwanese women. A case-control study was carried out to enroll 84 patients with breast cancer and 81 patients with benign breast disease. The subcellular localization of BRCA1 was examined using immunofluorescent assays on fresh tissue touch-imprinting slides to classify staining results into diffuse nuclear (DN), MN, and negative staining. Genetic variations of BRCA1 nuclear localization/transportation-related sequences were analyzed by cDNA sequencing of both nuclear localization signals (NLS) and nuclear export signals (NES). The BRCA1 antibody was verified by two other published ones. Comparisons of immunofluorescent assay with immunohistochemical and H&E staining methods were also performed. BRCA1 mislocalization conferred a 3.13-fold [95% confidence interval (CI): 1.31-7.50] risk of developing breast cancer for the MN form and a 5.79-fold (95% CI:1.58-21.23) risk for BRCA1-negative cases compared with DN staining. However, no genetic variant was found in the NES or the NLS region of the BRCA1 gene. In terms of prognosis, BRCA1 mislocalization showed a 3.5-fold (95% CI: 1.20-10.09) increased risk of breast cancer death compared with DN staining after adjusting for tumor node metastasis stage. BRCA1 MN forms and BRCA1-negative patterns led to a higher risk of carcinogenesis and a poor prognosis of breast cancer. Such BRCA1 mislocalization may not be directly caused by the genetic effects of the NLS and NES domains, but stem from nongenetic modifications (such as epigenetic silencing).

Transplantation of human dental pulp-derived stem cells protects against heatstroke in mice.

Stem cells from human exfoliated deciduous tooth pulp (SHED) is a promising approach for the treatment of stroke and spinal cord injury. In this study, we investigated the therapeutic effects of SHED for the treatment of multiple organ (including brain, particularly hypothalamus) injury in heatstroke mice. ICR male mice were exposed to whole body heating (WBH; 41.2°C, relative humidity 50-55%, for 1 h) and then returned to normal room temperature (26°C). We observed that intravenous administration of SHED immediately post-WBH exhibited the following therapeutic benefits for recovery after heatstroke: (a) inhibition of WBH-induced neurologic and thermoregulatory deficits; (b) reduction of WBH-induced ischemia, hypoxia, and oxidative damage to the brain (particularly the hypothalamus); (c) attenuation of WBH-induced increased plasma levels of systemic inflammatory response molecules, such as tumor necrosis factor-α and intercellular adhesion molecule-1; (d) improvement of WBH-induced hypothalamo-pituitary-adrenocortical (HPA) axis activity (as reflected by enhanced plasma levels of both adrenocorticotrophic hormone and corticosterone); and (e) attenuation of WBH-induced multiple organ apoptosis as well as lethality. In conclusion, post-WBH treatment with SHED reduced induction of proinflammatory cytokines and oxidative radicals, enhanced plasma induction of both adrenocorticotrophic hormone and corticosterone, and improved lethality in mouse heatstroke. The protective effect of SHED may be related to a decreased inflammatory response, decreased oxidative stress, and an increased HPA axis activity following the WBH injury.

Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage.

Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1ß, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage) in mice.

Umbilical cord blood-derived stem cells improve heat tolerance and hypothalamic damage in heat stressed mice.

Heatstroke is characterized by excessive hyperthermia associated with systemic inflammatory responses, which leads to multiple organ failure, in which brain disorders predominate. This definition can be almost fulfilled by a mouse model of heatstroke used in the present study. Unanesthetized mice were exposed to whole body heating (41.2°C for 1 hour) and then returned to room temperature (26°C) for recovery. Immediately after termination of whole body heating, heated mice displayed excessive hyperthermia (body core temperature ~42.5°C). Four hours after termination of heat stress, heated mice displayed (i) systemic inflammation; (ii) ischemic, hypoxic, and oxidative damage to the hypothalamus; (iii) hypothalamo-pituitary-adrenocortical axis impairment (reflected by plasma levels of both adrenocorticotrophic-hormone and corticosterone); (iv) decreased fractional survival; and (v) thermoregulatory deficits (e.g., they became hypothermia when they were exposed to room temperature). These heatstroke reactions can be significantly attenuated by human umbilical cord blood-derived CD34(+) cells therapy. Our data suggest that human umbilical cord blood-derived stem cells therapy may improve outcomes of heatstroke in mice by reducing systemic inflammation as well as hypothalamo-pituitary-adrenocortical axis impairment.

Decrease of PPARδ in Type-1-Like Diabetic Rat for Higher Mortality after Spinal Cord Injury.

Changes in the peroxisome proliferator-activated receptors- δ (PPAR δ ) expression in rats after spinal cord injury (SCI) have been previously reported. Diabetic animals show a higher mortality after SCI. However, the relationship between the progress of diabetes and PPAR δ in SCI remains unknown. In the present study, we used compressive SCI in streptozotocin-(STZ-) induced diabetic rats. GW0742, a PPAR δ agonist, was used to evaluate its merit in STZ rats after SCI. Changes in PPAR δ expression were detected by Western blot. Survival rates were also estimated. A lower expression of PPAR δ in spinal cords of STZ-diabetic rats was observed. In addition, the survival times in two-week induction diabetes were longer than those in eight-week induction group, which is consistent with the expression of PPAR δ in the spinal cord. Moreover, GW0742 significantly increased the survival time of STZ rats. Furthermore, their motor function and pain response were attenuated by GSK0660, a selective PPAR δ antagonist, but were enhanced by GW0742. In conclusion, the data suggest that higher mortality rate in STZ-diabetic rats with SCI is associated with the decrease of PPAR δ expression. Thus, change of PPAR δ expression with the progress of diabetes seems responsible for the higher mortality rate after SCI.

End-stage renal disease after hypertensive disorders in pregnancy.

OBJECTIVE: The purpose of this study was to determine the long-term postpartum risk of end-stage renal disease in women with hypertensive disorders in pregnancy. Although most women with hypertensive disorders in pregnancy recover after delivery, some may experience acute renal failure. STUDY DESIGN: We searched Taiwan's National Health Insurance Research Database to identify women with hypertensive disorders in pregnancies and deliveries between 1998 and 2002. All cases were followed for a maximum of 11 years (median, 9 years; interquartile range, 7.79-10.02 years) to estimate the incidence of end-stage renal disease; Cox regression analysis that was adjusted for potential confounding was used to determine the relative risk. RESULTS: Of the 13,633 women with hypertensive disorders in pregnancy, 46 experienced end-stage renal disease. Women with hypertensive disorders in pregnancy had a risk of end-stage renal disease that was 10.64 times greater than did women without them (95% confidence interval [CI], 7.53-15.05). The risk was highest in women with a history of preeclampsia superimposed on chronic hypertension (hazard ratio, 44.72; 95% CI, 22.59-88.51). Women with gestational hypertension had a higher risk of end-stage renal disease than did women without hypertensive disorders in pregnancy (hazard ratio, 5.82; 95% CI, 2.15-15.77). CONCLUSION: Women with hypertensive disorders in pregnancy have a higher risk of postpartum end-stage renal disease, regardless of which type of hypertensive disorder they have. Women with a history of hypertensive disorders in pregnancy are encouraged to have regular postpartum checkups, especially of renal function.

Umbilical cord blood-derived CD34⁺ cells improve outcomes of traumatic brain injury in rats by stimulating angiogenesis and neurogenesis.

Human umbilical cord blood cells (HUCBCs) have been shown to be beneficial in reducing neurological deficits in rats with brain fluid percussion injury (FPI). This study aimed to assess the basic mechanisms underlying the neuroprotective effects of HUCBC-derived cluster of differentiation 34-positive (CD34⁺) cells. Rats were divided into three major groups: (i) sham-operated controls; (ii) FPI rats treated with phosphate-buffered saline (PBS); (iii) FPI rats treated with 0.2%, 50%, or 95% CD34⁺ cells (in 5 × 105 cord blood lymphocytes and monocytes). Intravenous (IV) administration of 0.3 ml of PBS, 0.2% CD34⁺ cells, 50% CD34⁺ cells, or 95% CD34⁺ cells was conducted immediately after FPI. It was found that 4 days post-FPI, CD34⁺ cells could be detected in the ischemic brain tissues for 50% CD34⁺ cell- or 95% CD34⁺ cell-treated FPI rats, but not for the PBS-treated FPI rats or the 0.2% CD34⁺ cell-treated FPI rats. CD34⁺ cell (0.2%)-treated FPI rats or PBS-treated FPI rats displayed neurological and motor deficits, cerebral contusion and apoptosis [e.g., increased numbers of both TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase-3-positive cells], and activated inflammation (e.g., increased serum levels of tumor necrosis factor-α). FPI-induced neurological motor dysfunction, cerebral contusion and apoptosis, and activated inflammation could be attenuated by 50% CD34⁺ or 95% CD34⁺ cell therapy. In addition 50% or 95% CD34⁺ cell therapy but not PBS or 0.2% CD34⁺ cell therapy significantly promoted angiogenesis (e.g., increased numbers of both vasculoendothelial growth factor-positive cells and 5-bromodeoxyuridine (BrdU)-endothelial double-positive cells), neurogenesis (e.g., increased numbers of both glial cell line-derived neurotrophic factor-positive cells and BrdU/neuronal nuclei double-positive cells) in the ischemic brain after FPI, and migration of endothelial progenitor cells from the bone marrow. Our data suggest that IV administration of HUCBC-derived CD34⁺ cells may improve outcomes of FPI in rats by stimulating both angiogenesis and neurogenesis.

Ischemic and oxidative damage to the hypothalamus may be responsible for heat stroke.

The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1ß and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.

Multidisciplinary examination for prenatal diagnosis of posterior cervical teratoma in early second trimester.

OBJECTIVE: Cervical teratomas represent approximately 3% of all congenital teratomas, which occur in approximately 1 in 20,000-40,000 live births. In this report, we present a case of congenital posterior cervical teratoma diagnosed by a two-dimensional (2D) ultrasound in the early second trimester. CASE REPORT: A 28-year-old woman, gravid 1, para 0, came to our prenatal clinic at 20 weeks of gestation for her first prenatal visit. Results of an ultrasound revealed a fetus with multiple cystic septal mass with internally calcified spots measuring approximately 3 cm over the left fetal neck. Because no other abnormality was noted at that time, magnetic resonance imaging (MRI) and amniocentesis were scheduled on the following day. At the same time, results of a 4D ultrasound revealed the mass size to be same as that measured by the 2D ultrasound; however, the location was defined on the left posterior neck and MRI showed there was no invasion to the intracranial area. The parents opted to continue the pregnancy. In the following prenatal cares, no polyhydramnios was found and the fetal body weight was within the normal growth curve. The baby was delivered by cesarean section at 38 weeks of gestation with Apgar scores of 8 (at 1 minute) and 9 (at 5 minutes). The baby was scheduled for surgical intervention 3 days after birth. Finally, results of a pathological analysis revealed the mass to be a benign cystic teratoma. CONCLUSION: Prenatal diagnosis of cervical teratoma is very crucial, allowing early detection of masses that obstruct the airway. Therefore, a multidisciplinary examination and follow-up are recommended for early prenatal diagnosis.

Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects.

OBJECTIVE: We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-α (TNF-α) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E2 (PGE2) induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The microdialysis probes were stereotaxically and chronically implanted into the hypothalamus of rabbit brain for determining extracellular levels of glutamate, hydroxyl radials, and PGE2. In addition, both the body core temperature and plasma levels of TNF-α were measured. RESULTS: All the body core temperature, plasma levels of TNF-α, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 were up-graded by an intravenous dose of LPS (2 µg/kg). Pretreatment with intravenous TMP (10-40 mg/kg) or intracerebroventricular TMP (130 µg in 20 µl per animal) 1 h before LPS administration significantly attenuated the LPS-induced fever as well as the increased hypothalamic levels of glutamate, hydroxyl radicals, and PGE2. LPS-induced fever could also be attenuated by intravenous or intracerebroventricular TMP 1 h after LPS injection. CONCLUSION: TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-α as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 in rabbits.

Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice.

Flutamide has been used as an adjunct for decreasing the mortality from subsequent sepsis. Heatstroke resembles septic shock in many aspects. We hypothesized that heat-induced multiple organ dysfunction syndromes and lethality could be reduced by flutamide therapy. In heatstroke groups, mice were exposed to whole body heating (41.2°C, for 1h) in a controlled-environment chamber. The heat-stressed mice were returned to normal room temperature (24°C) after whole body heating. Mice still alive on day 4 of WBH treatment were considered survivors. Physiological and biochemical parameters were monitored for 2.5h post-WBH. Heatstroke mice were subcutaneously treated with flutamide (12.5-50mg/kg body weight in 0.05 ml) or vehicle solution (0.05 ml/kg body weight) once daily for 3 consecutive days post-WBH. We evaluated the effect of flutamide in heatstroke mice and showed that flutamide significantly (i) attenuated hypothermia, (ii) reduced the number of apoptotic cells in the hypothalamus, the spleen, the liver, and the kidney, (iii) attenuated the plasma index of toxic oxidizing radicals (e.g., nitric oxide metabolites and hydroxyl radicals), (iv) diminished the plasma index of the organ injury index (e.g., lactate dehydrogenase), (v) attenuated plasma systemic inflammation response molecules (e.g., tumor necrosis factor-α and interleukin-6), (vi) reduced the index of infiltration of polymorphonuclear neutrophils in the lung (e.g., myeloperoxidase activity), and (vii) allowed three times the fractional survival compared with vehicle. Thus, flutamide appears to be a novel agent for the treatment of mice with heatstroke or patients in the early stage of heatstroke.

Mediation of vagal cardioinhibitory responses by glutamatergic receptors in the caudal medulla of turtles.

Our previous studies showed that electrical stimulation of the nuclei ambiguous (NA) or dorsomotor nuclei of the vagus (DMV) complex in the brain stem of spontaneously breathing pond turtles (Cyclemys fiavomarginata), anesthetized with chloralose (4 mg/100 g) and urethane (40 mg/100 g), produced a marked slowing or even cessation of the heart rate, and resulted in an immediate fall of blood pressure. Results of the present study further demonstrated that the cardioinhibitory responses could also be elicited by microinjection of monosodium glutamate (0.2-20 nl, 50 mM) into the NA/DMV complex in turtles. A two-barrel glass micropipette held in a manipulator was connected to a pneumatic pressure pump for microinjection. The glutamate-induced cardioinhibitory responses could be significantly reduced in a dose-dependent manner by pretreatment with AP-5 (a NMDA receptor antagonist, at 1-8 nmole) or CNQX (a non-NMDA receptor antagonist; at 0.1-0.8 nmole) 20 min before glutamate administration. Histochemical verification by injecting horseradish peroxidase into the cervical vagus nerves revealed that retrogradely labeled glutamatergic neurons in the NA/DMV complex were observed. These results suggest that glutamatergic receptors in the caudal medulla may mediate vagal cardioinhibitory responses in the turtle.

A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats.

Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 µg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke.

AIM: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. METHODS: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. RESULTS: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 levels during heatstroke. CONCLUSION: Our results suggest that systemic delivery of kynurenic acid may attenuate multiorgan dysfunction in rats after heatstroke.