[The mediating effect of perceived social support in the relationship between maternal personality traits and pregnancy-related anxiety].

Objective: Exploring the mediating effect of perceived social support between the maternal personality traits and pregnancy-related anxiety. Methods: Singleton pregnant women who underwent antenatal checkups in the obstetrics department of general hospital affiliated to Ningxia Medical University from July to December 2021 were enrolled in this study to investigate perceived social support, pregnancy-related anxiety and conscious personality traits. Pearson correlation analysis was used to analyze the association between the maternal personality traits, perceived social support, and pregnancy-related anxiety, and the mediating effect of perceived social support was analyzed using Bootstrap method. Results: A total of 1 259 subjects were included in the study, of which 170 (13.50%) pregnant women felt introverted. The total score of perceived social support was (46.37±8.38), and 31.45% of pregnant women had high perceived social support. The total score of pregnancy-related anxiety was (21.48±5.53). The score of worry about fetal health was (10.09±3.24), and 368 (29.23%) of pregnant women had pregnancy-related anxiety. Maternal personality traits and pregnancy-related anxiety were negatively correlated (r=-0.076, P<0.05) and positively correlated with perceived social support during pregnancy (r= 0.127, P<0.05). Perceived social support during pregnancy and pregnancy-related anxiety were negatively correlated (r=-0.236, P<0.05). Perceived social support partially mediated the relationship between the maternal personality traits and pregnancy-related anxiety, with a relative effect value of 37.50%. Conclusion: The maternal personality traits, level of perceived social support and pregnancy-related anxiety are all related. Perceived social support could mediate the relationship between the maternal personality traits and pregnancy-related anxiety.

[Clinical features and advanced progress of secondary BPPV].

BPPV is a disease provoked by abrupt head movements, results in short paroxysmal vertigo or nystagmus. These patients often can accurately describe the dizziness happened when they head move suddenly, especially when looking upward, turning over in bed, lying down, or bending over. BPPV is divided into idiopathic BPPV and secondary BPPV, in most cases. The underlying cause cannot be determined, which is called idiopathic; however, in 30% patients, BPPV may be attributed to a specific cause and is termed secondary BPPV. We reviewed the pathogenesis, mechanisms, clinical features, treatment and the latest progress of secondary BPPV.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation.

This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

Magnetism-Driven Ferroelectricity in Double Perovskite Y2NiMnO6.

We report the discovery of multiferroic behavior in double perovskite Y2NiMnO6. X-ray diffraction shows that the material has a centrosymmetric crystal structure of space group P2(1)/n with Ni(2+)/Mn(4+) ordering. This result is further confirmed by aberration-corrected scanning transmission electron microscopy combined with atomic resolution electron energy loss spectroscopy. The appearance of ferroelectric polarization coincides with the magnetic phase transition (∼67 K), which indicates that the ferroelectricity is driven by magnetism, and this is further confirmed by its strong magnetoelectric (ME) effect. We proposed the origin of the ferroelectricity is associated with the combination of Ni(2+)/Mn(4+) charge ordering and the ↑↑↓↓ spin ordering. When compared with other known magnetic multiferroics, Y2NiMnO6 displays several attractive multiferroic properties, including high polarization (∼145 µC/m(2)), a high multiferroic transition temperature (∼67 K), and strong ME coupling (∼21%).

Evolution and functions of stanniocalcins in cancer.

Stanniocalcin (STC), first isolated from the corpuscles of stannius of teleost fishes, was originally known for its regulation on calcium/phosphate transport. Increasing evidence demonstrates that STCs display the important function in some physiological and pathological behaviors such as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, nerve diseases, etc. Moreover, STCs are implicated in the development and progression of multiple malignancies through promoting cell growth, proliferation, invasion, metastasis, and apoptotic escape. Some studies have shown that NF-κB upregulates STC expression, thereby activating the downstream HIF-1/ERK1/2 signaling pathway, enhancing the transcriptional activity of tumor-related factors (MMP-2/9, cyclinD1, Bcl-2, N-cadherin, etc) and contributing to tumorigenesis. Here, this brief review describes recent progress of STCs in mammalians, focused mainly on their critical functions in cancer.

Link of obesity and gastrointestinal cancer: crossroad of inflammation and oxidative stress.

Obesity incidence has reached pandemic levels, and is accompanied by high incidence and poor prognosis of various types of cancers including gastrointestinal ones. Underlying mechanisms include elevated levels of insulin, IGF-I, and altered adipokine concentration, mainly towards leptin and adiponectin levels. However, it is not yet thoroughly understood. It is now widely known that obesity is associated with chronic low-grade inflammation, characteristic of altered immune cell infiltration in adipose tissue, and changed inflammatory cytokines and chemokines: tumor necrosis factor alpha (TNF-a), IL-6, and the chemoattractant monocyte chemoattractant protein 1 (MCP-1) and others, all together eventually promoting caner pathogenesis. Moreover, accumulating reports have shown that excess adipose tissue in obese individuals resulted in elevated levels of systematic oxidative stress, another way of promoting cancer development and progression. In general, altered immunological milieu and oxidative stress in obesity are important determinants for tumorigenesis.

Clinical significance of hmgb1 expression in human gastric cancer.

High mobility group box 1 (HMGB1) has been proved to be implicated in a variety of cell physiological and pathological behaviors including immune response, inflammation and cancer. Accumulating evidence suggests that HMGB1 plays a critical role in the development and progression of multiple malignancies. However, the clinical significance and prognosis of HMGB1 expression in some cancers remain controversial. The present study aimed to investigate whether overexpression of HMGB1 is an independent prognostic factor in patients with gastric cancer. The correlation of HMGB1 expression with clinicopathologic characteristics and prognosis was assessed by immunohistochemical assay through tissue microarray procedure in 50 primary gastric cancer cases. Our results indicated that the positive expression of HMGB1 was significantly increased in the nucleus of gastric cancer tissues compared with the adjacent non-cancerous tissues (ANCT) (64.0% vs 44.0%, P=0.025), but was not linked to the clinicopathologic features, including the TNM stage (P=0.533) and metastatic lymph node (P=0.771), in patients with gastric cancer. Kapalan-Meier and log-rank analysis demonstrated that overexpression of HMGB1 did not exert significant impact on the overall survival of patients with gastric cancer (P=0.805). Furthermore, Cox regression analysis showed that high HMGB1 protein expression did not represent an independent risk factor for patients with gastric cancer (P=0.677). Taken together, our findings suggest that high expression of HMGB1 is not correlated with the clinicopathologic characteristics of gastric cancer, and cannot serve as an independent prognostic biomarker for patients with gastric cancer.

IL-10 treatment is associated with prohibitin expression in the Crohn's disease intestinal fibrosis mouse model.

Prohibitin, which can inhibit oxidative stress and mitochondrial dysfunction, has been shown to have significant anti-inflammatory activities. Here, we investigate the effects of altering prohibitin levels in affected tissues in the interleukin-10 knockout (IL-10KO) mouse model with intestinal fibrosis. The aim of this study is to investigate the effects of IL-10 on prohibitin and the role of prohibitin in intestinal fibrosis of murine colitis. After the mice were treated with IL-10, prohibitin expression and localization were evaluated in IL-10KO and wild-type (WT, 129/SvEv) mice. The colon tissue was then investigated and the potential pathogenic molecular mechanisms were further studied. Fluorescence-based quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry assays revealed a significant upregulation of prohibitin with IL-10 treatment. Furthermore, IL-10 decreases inflammatory cytokines and TGF-ß1 in the IL-10KO model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. In conclusion, we hypothesize that IL-10 treatment is associated with increased prohibitin and would decrease inflammation and fibrosis in an animal model of Crohn's disease. Interestingly, prohibitin may be a potential target for intestinal fibrosis associated with inflammatory bowel disease (IBD).

The Jahn-Teller effect in the electron momentum spectroscopy of ammonia.

The 1e and 3a(1) bands of the ammonia molecule have been studied using the high-resolution electron momentum spectroscopy at impact energies of 1200 and 600 eV. Several slices of 1e and 3a(1) bands in the different binding energy ranges were selected, and their electron-momentum distributions were carefully compared. The discernable difference among the distributions of the selected slices of the 1e band shows that the Jahn-Teller effect indeed influences the electron momentum distribution of the 1e orbital of ammonia.

Expression of Yes-associated protein in gastric adenocarcinoma and inhibitory effects of its knockdown on gastric cancer cell proliferation and metastasis.

Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels of YAP, proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown of YAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression of YAP was observed in 69.23 percent gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through down-regulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.

Clinicopathologic characteristics of YES-associated protein 1 overexpression and its relationship to tumor biomarkers in gastric cancer.

Yes-associated protein 1 (YAP1), a downstream effector of the Hippo pathway, plays an important role in the development and progression of multiple malignancies, including human gastric cancer (GC). However, the clinical significance of YAP1 expression in GC needs to be comprehensively explored. Based on the pivotal role of YAP1 in the hippo pathway, we explored the clinicopathologic characteristics of YAP1 overexpression and its relationship to some tumor biomarkers in GC. Ninety cases of GC, chronic gastritis (CG) and CG with dysplasia samples were collected, and clinical data of all patients with GC were analyzed. The expression of YAP1 was assessed using immunohistochemical assay in biopsy samples. As a result, almost all the GC samples, but few CG and dysplasia samples showed YAP1 positive staining mainly in the nucleus. The expression of YAP1 was found in GC tissues with higher strong reactivity rate, compared with dysplasia and CG tissues (79.2 percent vs 47.1 percent and 15 percent, each P<0.001), and its expression level was elevated with the ascending order of GC malignancy. However, no significant correlation was found between the expression of YAP1 and epidermal growth factor receptor (EGFR) with gender, age, gross stage, degree of differentiation, tumor size, TNM staging, perineural infiltration, vascular invasion, lymphatic vessel invasion and lymph node metastases in patients with GC (each P>0.05). Furthermore, Spearman rank correlation analysis also showed no correlation of YAP1 with EGFR, Ki-67, CD34 and topoisomerase II (TOP II). Taken together, YAP1 is highly expressed in GC tissues compared with the dysplasia and CG tissues and its expression level is elevated with the ascending order of tumor malignancy; but, YAP1 expression does not correlate with the clinicopathologic characteristics and the expression of EGFR, Ki-67, CD34 and TOP II in GC.

Identification of differentially-expressed proteins between early submucosal non-invasive and invasive colorectal cancer using 2D-DIGE and mass spectrometry.

Early detection and diagnosis of colorectal cancer (CRC) are closely related to a better therapeutic outcome, and the five-year survival rate of early CRC is over 90 percent. Though endoscopic minimally invasive treatment has become a quick and effective therapy for early CRC, endoscopic biopsies are usually not deep enough to obtain tissues from the submucosal layer and it is difficult to determine whether early CRC has infiltrated into the submucosa. Therefore, in the present study, we constructed tumor models of early submucosal non-invasive CRC (SNICRC) and submucosal invasive CRC (SICRC) in Fischer-344 rats induced by N-methyl-N-nitrosourea (MNU). The differentially-expressed proteins were analyzed and identified in SNICRC, SICRC and normal control (NC) tissues using highly sensitive two dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Proteomic data revealed 132 protein spots between SNICRC and SICRC, 162 protein spots between SICRC and NC and 154 protein spots between SNICRC and NC which were found differentially expressed. These differential spots were picked, in-gel digested and peptide mass fingerprints were obtained by MALDITOF-MS/MS. Finally, five differentially-expressed proteins in SNICRC, SICRC and NC were identified, and increases in Transgelin, peptidylprolyl isomerase A (PPIA) and tropomyosin alpha isoform d were observed, while decreases in carbonic anhydrase 2 (CAII) and an unnamed protein were detected in SICRC compared with SNICRC and NC. Furthermore, Fluorescence-based quantitative polymerase chain reaction (FQ-PCR), Western blotting and immunohistochemistry assays also revealed significant upregulation of Transgelin expression and down-regulation of CAII expression in SICRC tissues. In conclusion, 2D-DIGE is confirmed to be an efficient strategy that enables us to identify differentially expressed proteins between early SNICRC and SICRC. The potential biomarkers such as Transgelin and CAII may be used for the detection of early SICRC.

CordyMax Cs-4 improves steady-state bioenergy status in mouse liver.

OBJECTIVE: To evaluate effects of CordyMax Cs-4, a mycelial fermentation product of Cordyceps sinensis, on energy metabolism. DESIGN: An in vivo pharmacology study using 31P nuclear magnetic resonance (NMR) spectroscopy. SUBJECTS AND STUDY INTERVENTIONS: Adult male C57-BL/6 mice were given an aqueous extract of CordyMax, 200 or 400 mg/kg per day or placebo for 7 days. OUTCOME MEASUREMENTS: Using 31P-NMR spectroscopy to measure cellular triphosphates and inorganic phosphate, expressed as a ratio to a reference peak, and calculate tissue pH. RESULTS: Steady-state beta adenosine triphosphate (ATP) increased in the liver of mice that received CordyMax (200 or 400 mg/kg per day) for 7 days, by 12.3% +/- 0.8% and 18.4% +/- 0.9%, respectively, compared to placebo controls (both p < 0.001), suggesting a higher hepatic bioenergy status in CordyMax-treated animals. Hepatic inorganic phosphate (Pi) decreased by 24.5% +/- 0.9% and 17.6% +/- 1.7% in the two treatment groups, respectively, compared to placebo controls (p < 0.001). The ratio of beta-ATP:Pi increased by 47.7% +/- 1.6% and 41.4% +/- 2.4%, respectively, in the treatment groups (both p < 0.001 compared to placebo). After discontinuation of CordyMax for 7 days, beta-ATP and Pi returned towards baseline. CONCLUSION: CordyMax is effective in improving bioenergy status in the murine liver, suggesting a mechanism underlying the known clinical effectiveness of CordyMax in alleviating fatigue and improving physical endurance, especially in elderly subjects.

Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance.

Studies from our laboratory using acute pharmacologic blockade of nitric oxide synthase (NOS) activity have suggested that nitric oxide (NO) has an important role in regulating carbohydrate metabolism. We now report on insulin sensitivity in mice with targeted disruptions in endothelial NOS (eNOS) and neuronal NOS (nNOS) genes compared with their wild-type (WT) counterparts. Mice underwent hyperinsulinemic-euglycemic clamp studies after a 24-h fast, during an insulin infusion of 20 mU x kg(-1) x min(-1). Glucose levels were measured at baseline and every 10 min during the clamp. Insulin levels were measured at baseline and at the end of the clamp study. Glucose infusion rates (GIRs) during the last 30 min of the clamp study were in a steady state. Tritiated glucose infusion was used to measure rates of endogenous glucose output (EGO) both at baseline and during steady-state euglycemia. Glucose disposal rates (GDRs) were computed from the GIR and EGO. Fasting and steady-state glucose and insulin levels were comparable in the 3 groups of mice. No differences in fasting EGO were noted between the groups. GIR was significantly reduced (37%, P = 0.001) in the eNOS knockout (KO) mice compared with the WT mice, with values for the nNOS mice being intermediate. EGO was completely suppressed in the nNOS and WT mice during insulin infusion, but not in the eNOS mice. Even so, the eNOS mice displayed significantly reduced whole-body GDRs compared with those of the WT mice (82.67+/-10.77 vs. 103.67+/-3.47 mg x kg(-1) x min(-1), P = 0.03). eNOS KO mice are insulin resistant at the level of the liver and peripheral tissues, whereas the nNOS KO mice are insulin resistant only in the latter. These data indicate that NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and that the eNOS isoform may play a dominant role relative to nNOS.

Dose-response relationship of insulin to glucose fluxes in the awake and unrestrained mouse.

The purpose of the study was to use the hyperinsulinemic-euglycemic clamp technique to generate insulin dose-response curves for insulin suppression of endogenous glucose output (EGO) and stimulation of the glucose disposal rate (GDR) in conscious unstressed mice. Five groups of male ICR (Institute for Cancer Research) mice were studied (N = 43). The animals underwent surgery for implantation of a jugular vein catheter 2 to 3 days before the clamp and were fasted 6 hours before the study. Each group was clamped at a different insulin infusion rate of 0, 2.5, 10, or 20 mU/kg/min. 3H-3-glucose was infused for measurement of the glucose turnover rate (rate of appearance [Ra]). Blood samples were collected by milking a severed tail-tip. EGO was calculated as the difference between the Ra and glucose infusion rate (GIR), and the glucose clearance rate (GCR) as the GDR divided by the plasma glucose concentration. From the curves generated, half-maximal EGO and GCR were obtained at a plasma insulin concentration of 20 to 30 microU/mL, which was achieved at an insulin infusion rate of about 4 to 5 mU/kg/min. Maximal suppression of EGO and stimulation of the GCR occurred at an insulin infusion rate of 10 mU/kg/min. The establishment of normative curves for insulin-stimulated glucose metabolism in conscious mice facilitates the evaluation of glucose metabolism in a variety of mouse models of insulin resistance.

Glucosamine infusion in rats rapidly impairs insulin stimulation of phosphoinositide 3-kinase but does not alter activation of Akt/protein kinase B in skeletal muscle.

Glucosamine, a metabolite of glucose via the hexosamine biosynthetic pathway, potently induces insulin resistance in skeletal muscle by impairing insulin-induced GLUT4 translocation to the plasma membrane. Activation of phosphoinositide (PI) 3-kinase is necessary for insulin-stimulated GLUT4 translocation, and the serine/threonine kinase Akt/protein kinase B (PKB) is a downstream mediator of some actions of PI 3-kinase. To determine whether glucosamine-induced insulin resistance could be due to impaired signaling, we measured insulin receptor substrate (IRS)-1 and insulin receptor tyrosine phosphorylation; PI 3-kinase activity associated with IRS-1, IRS-2, and phosphotyrosine; and Akt activity and phosphorylation in skeletal muscle of rats infused for 2 h with glucosamine (6.0 mg x kg(-1) x min(-1)) or saline. Euglycemic-hyperinsulinemic clamp studies (12 mU x kg(-1) x min(-1) insulin) in awake rats showed that glucosamine infusion resulted in rapid induction of insulin resistance, with a 33% decrease in glucose infusion rate (P < 0.01). Tissues were harvested after saline alone (basal), 1 min after an insulin bolus (10 U/kg), or after 2 h of insulin clamp in saline- and glucosamine-infused rats. After 1 min of insulin stimulation, phosphorylation of IRS-1 and insulin receptor increased 6- to 8-fold in saline-infused rats and 7- to 10-fold in glucosamine-infused rats. In saline-infused rats, 1 min of insulin stimulation increased PI 3-kinase activity associated with IRS-1, IRS-2, or phosphotyrosine 7.6-, 6.4-, and 10-fold, respectively. In glucosamine-infused rats treated for 1 min with insulin, PI 3-kinase activity associated with IRS-1 was reduced 28% (P < 0.01) and that associated with phosphotyrosine was reduced 43% (P < 0.01). Insulin for 1 min stimulated Akt/PKB activity approximately 5-fold in both saline- and glucosamine-infused rats; insulin-induced hyperphosphorylation of Akt/PKB was not different between groups. Glucosamine infusion alone had no effect on tyrosine phosphorylation of the insulin receptor or IRS-1 or on stimulation of PI 3-kinase or Akt/PKB activity. However, 2 h of insulin clamp reduced PI 3-kinase activity associated with IRS-1, IRS-2, or phosphotyrosine to <30% of that seen with 1 min of insulin. No effect of glucosamine was seen on these signaling events when compared with 2 h of insulin clamp without glucosamine. Our data show that 1) glucosamine infusion in rats is associated with an impairment in the early activation of PI 3-kinase by insulin in skeletal muscle, 2) this insulin-resistant state does not involve alterations in the activation of Akt/PKB, and 3) prolonged insulin infusion under clamp conditions results in a blunting of the PI 3-kinase response to insulin.

A technique for assessing the effects of olfaction on feed preference in lactating Holstein cows.

Our objective was to develop a method for assessing the effects of olfaction on feed preference. Two multiparous lactating Holstein cows were offered a totally mixed ration consisting of corn silage, alfalfa haylage, and a ground corn and soybean meal-based concentrate mixture (25:25:50 on a DM basis) for their ad libitum consumption in four consecutive 2.5-h periods daily for 5 d. An apparatus was developed that allowed odorants to be distributed at a set rate over two feeding containers with limited possibility of odor carryover. Four odorants and a control (no odorant) were compared against each other. All possible comparisons were conducted on the left and right feeding sides to avoid potential lateral-preference effects. Rank values of 0 or .5 were assigned to each odorant based on the percentage of total feed consumed in a period. A test of overall equality based on the sums of squares of ranks was used to determine whether odors affected preference. The limited results indicated that inhalation of odorants did not affect preference. Rank values were doubled for several odorants when compared with others, which suggested that the sample size limited experimental sensitivity. To attain reasonable power, we estimated that at least six cows were needed per study. Large effects of odorants on feed preference would have been required to reach statistical significance in this trial; however, the method provides a practical technique for testing the effects of olfaction on feed preference in cattle when the suggested number of cows is used.

The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I.

This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal.

Central nervous system nitric oxide synthase activity regulates insulin secretion and insulin action.

Systemic inhibition of nitric oxide synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) causes acute insulin resistance (IR), but the mechanism is unknown. We tested whether L-NMMA-induced IR occurs via NOS blockade in the central nervous system (CNS). Six groups of Sprague-Dawley rats were studied after chronic implantation of an intracerebroventricular (ICV) catheter into the lateral ventricle and catheters into the carotid artery and jugular vein. Animals were studied after overnight food deprivation, awake, unrestrained, and unstressed; all ICV infusion of L-NMMA or D-NMMA (control) were performed with artificial cerebrospinal fluid. ICV administration of L-NMMA resulted in a 30% rise in the basal glucose level after 2 h, while ICV D-NMMA had no effect on glucose levels. Insulin, epinephrine, and norepinephrine levels were unchanged from baseline in both groups. Tracer (3H-3-glucose)-determined glucose disposal rates during 2 h euglycemic hyperinsulinemic (300 microU/ml) clamps performed after ICV administration of L-NMMA were reduced by 22% compared with D-NMMA. Insulin secretory responses to a hyperglycemic clamp and to a superimposed arginine bolus were reduced by 28% in L-NMMA-infused rats compared with D-NMMA. In conclusion, ICV administration of L-NMMA causes hyperglycemia via the induction of defects in insulin secretion and insulin action, thus recapitulating abnormalities observed in type 2 diabetes. The data suggest the novel concept that central NOS-dependent pathways may control peripheral insulin action and secretion. This control is not likely to be mediated via adrenergic mechanisms and could occur via nonadrenergic, noncholinergic nitrergic neural and/or endocrine pathways. These data support previously published data suggesting that CNS mechanisms may be involved in the pathogenesis of some forms of insulin resistance and type 2 diabetes independent of adiposity.