Biomechanical behaviour of a French femoral component with thin cement mantle: The 'French paradox' may not be a paradox after all.

OBJECTIVE: Cement thickness of at least 2 mm is generally associated with more favorable results for the femoral component in cemented hip arthroplasty. However, French-designed stems have shown favorable outcomes even with thin cement mantle. The biomechanical behaviors of a French stem, Charnley-Marcel-Kerboull (CMK) and cement were researched in this study. METHODS: Six polished CMK stems were implanted into a composite femur, and one million times dynamic loading tests were performed. Stem subsidence and the compressive force at the bone-cement interface were measured. Tantalum ball (ball) migration in the cement was analyzed by micro CT. RESULTS: The cement thickness of 95 % of the proximal and middle region was less than 2.5 mm. A small amount of stem subsidence was observed even with collar contact. The greatest compressive force was observed at the proximal medial region and significant positive correlation was observed between stem subsidence and compressive force. 9 of 11 balls in the medial region moved to the horizontal direction more than that of the perpendicular direction. The amount of ball movement distance in the perpendicular direction was 59 to 83% of the stem subsidence, which was thought to be slip in the cement of the stem. No cement defect and no cement breakage were seen. CONCLUSION: Thin cement in CMK stems produced effective hoop stress without excessive stem and cement subsidence. Polished CMK stem may work like force-closed fixation in short-term experiment.Cite this article: Y. Numata, A. Kaneuji, L. Kerboull, E. Takahashi, T. Ichiseki, K. Fukui, J. Tsujioka, N. Kawahara. Biomechanical behaviour of a French femoral component with thin cement mantle: The 'French paradox' may not be a paradox after all. Bone Joint Res 2018;7:485-493. DOI: 10.1302/2046-3758.77.BJR-2017-0288.R2.

The influence of cement thickness on stem subsidence and cement creep in a collarless polished tapered stem: When are thick cement mantles detrimental?

OBJECTIVES: Favourable results for collarless polished tapered stems have been reported, and cement creep due to taper slip may be a contributing factor. However, the ideal cement thickness around polished stems remains unknown. We investigated the influence of cement thickness on stem subsidence and cement creep. METHODS: We cemented six collarless polished tapered (CPT) stems (two stems each of small, medium and large sizes) into composite femurs that had been reamed with a large CPT rasp to achieve various thicknesses of the cement mantle. Two or three tantalum balls were implanted in the proximal cement in each femur. A cyclic loading test was then performed for each stem. The migration of the balls was measured three-dimensionally, using a micro-computed tomography (CT) scanner, before and after loading. A digital displacement gauge was positioned at the stem shoulder, and stem subsidence was measured continuously by the gauge. Final stem subsidence was measured at the balls at the end of each stem. RESULTS: A strong positive correlation was observed between mean cement thickness and stem subsidence in the CT slices on the balls. In the small stems, the balls moved downward to almost the same extent as the stem. There was a significant negative correlation between cement thickness and the horizontal:downward ratio of ball movement. CONCLUSION: Collarless polished tapered stems with thicker cement mantles resulted in greater subsidence of both stem and cement. This suggests that excessive thickness of the cement mantle may interfere with effective radial cement creep.Cite this article: E. Takahashi, A. Kaneuji, R. Tsuda, Y. Numata, T. Ichiseki, K. Fukui, N. Kawahara. The influence of cement thickness on stem subsidence and cement creep in a collarless polished tapered stem: When are thick cement mantles detrimental? Bone Joint Res 2017;6:-357. DOI: 10.1302/2046-3758.65.BJR-2017-0028.R1.

In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients.

BACKGROUND: The aetiology of ulcerative colitis is inadequately understood, and drug therapy has been empirical rather than based on sound understanding of disease aetiology. This has been a major factor for refractoriness and adverse drug effects as additional complications. However, ulcerative colitis by its very nature is exacerbated and perpetuated by inflammatory cytokines, which are released by peripheral granulocytes and monocytes as well. Additionally, active ulcerative colitis is often associated with elevated peripheral granulocytes and monocytes with activation behaviour and are found in vast numbers within the colonic mucosa. Hence, from the clinicopathologic viewpoint, granulocytes and monocytes are appropriate targets for therapy in ulcerative colitis. Based on this thinking, an Adacolumn has been developed for depleting excess granulocytes and monocytes by adsorption. METHODS: By colonoscopy, biopsy and histology, we investigated the impact of granulocyte and monocyte adsorption (GMA) on the mucosal level of granulocytes and monocytes in patients with active ulcerative colitis. Forty-five patients (26 steroid naïve and 19 steroid-dependent), mean age 44.7 yr, were included. Twenty patients had total colitis and 25 had left-sided colitis. Each patient was given up to 11 GMA sessions over 12 weeks. No patient received additional medications within 4 weeks (steroid) to 8 weeks (other immunosuppressants) prior to entry or during the GMA course. Colonoscopy together with biopsy was done at entry and within 2 weeks after the last GMA session. RESULTS: At entry, the mean clinical activity index was 12.6; range 10-16. A total of 400 colonic biopsies were examined, which revealed massive infiltration of the colonic mucosa by granulocytes, and GMA was associated with striking reduction of granulocytes in the mucosa. At week 12, 33 of 45 patients (73.3%, P<0.01) had achieved clinical remission (the mean clinical activity index

Risk factors for clustering of tuberculosis cases: a systematic review of population-based molecular epidemiology studies.

BACKGROUND: Many molecular epidemiology studies have been conducted to identify risk factors for clustering of tuberculosis (TB) cases in the population. OBJECTIVE: To estimate the impact of commonly investigated risk factors on TB clustering. METHODS: Ten electronic databases were searched up to January 2006 along with a hand search of the International Journal of Tuberculosis and Lung Disease and bibliographies of review articles. Meta-analyses of odds ratios (ORs) for various risk factors were conducted using random effect models, stratified by TB incidence. Meta-regressions were employed to account for the heterogeneity in clustering proportions and the magnitudes of risk. FINDINGS: The TB clustering proportion varied greatly (7.0-72.3%) among 36 studies in 17 countries. In multiple meta-regression analyses, high TB incidence, mean cluster size and conventional contact tracing were significantly associated with higher clustering. The pooled ORs (95%CIs) for low and high/intermediate TB incidence studies, using a cut off of 25/100000 per year, were 3.4 (2.7- 4.2) and 1.6 (1.3-2.1) for local-born status, 1.6 (1.5-1.7) and 1.7 (1.3-2.2) for pulmonary TB and 1.2 (1.1-1.3) and 1.3 (1.1-1.7) for smear-positive cases, respectively. Male sex, local birth, alcohol abuse and injection drug use were significantly higher risks in low TB incidence studies than in the high/intermediate ones. INTERPRETATION: Meta-analyses yielded significant estimates of ORs for several risk factors across both levels of TB incidence. Alcohol abuse, injection drug use and homelessness--all characteristics of marginalized populations--were found to be consistently significant in populations of low TB incidence. More research is needed to better understand TB transmission dynamics in high-burden countries.

Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas.

BACKGROUND: Previously, we indicated that stromal genetic instability might contribute to tumorigenesis of both sporadic and ulcerative colitis associated colorectal adenocarcinomas. Considering the established adenoma-adenocarcinoma sequence, in this study we analysed genetic instability in colorectal adenoma cells and surrounding stroma. METHODS: In 164 colorectal tumours (34 hyperplastic polyps, 38 tubular adenomas with low grade dysplasia (TA-L), 51 tubular adenomas with high grade dysplasia (TA-H), and 41 invasive carcinomas), epithelial and stromal genetic instability with National Cancer Institute standard microsatellite markers and chromosome 17 (Chr17) markers, were analysed by a combination of laser capture microdissection and GeneScan approaches. RESULTS: While frequencies of both loss of heterozygosity (LOH) and microsatellite instability (MSI) were extremely low in hyperplastic polyps, LOH in tubular adenomas was detected in both epithelial (TA-L 13.2%, TA-H 27.5%) and stromal (5.3% and 5.9%, respectively) elements, along with MSI (5.3% and 13.7%, and 5.3 and 5.9%, respectively). Frequencies of epithelial alterations were higher in TA-H than in TA-L, and greatest in the carcinoma group. On the other hand, frequencies of stromal LOH or MSI were almost constant (5.3% approximately 17.1%, 5.3% approximately 17.1%, respectively) in adenomas and invasive carcinomas. In addition, p53 was found to be significantly overexpressed in a greater proportion of TA-L with LOH than in those without genetic instability. CONCLUSION: The results indicate the presence of genetic alterations in stroma from an early stage of carcinogenesis, accompanied by stepwise increasing genetic instability of epithelia with progression to cancer. Thus microenvironmental changes due to genetic alteration in Chr17 markers in stromal cells may play an important role in colon adenoma and adenocarcinoma development.

Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1.

OBJECTIVES: To clarify the dynamics of molecules composing the blood-nerve barrier (BNB) in inflammatory neuropathies. METHODS: The expression of four tight junction (TJ) proteins-claudin-1, claudin-5, occludin, and ZO-1-was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). RESULTS: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. CONCLUSIONS: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB.

Possible alternative carcinogenesis pathway featuring microsatellite instability in colorectal cancer stroma.

Differential microsatellite instability (MSI) in tumour epithelial and stromal compartments has not been well examined for colorectal cancers. Using laser-captured microdissection, separate specimens of these compartments of 40 sporadic colorectal cancers were sampled and MSI was tested with four markers. To examine the relation between the MSI phenotype in the stroma and other genetic events and histopathological features, p53 and K-ras gene mutations were analysed, and the expression of p53, hMLH1, and hMSH2 protein was determined by immunohistochemistry. Microsatellite instability positive results were obtained for both epithelium (34%) and stromal tissue (41%). While MSI in epithelium correlated with differentiation and Dukes' stage, that in stroma demonstrated an inverse relation, being particularly frequent in well-differentiated adenocarcinomas (54%) and Dukes' A lesions (55%). Further, a significant inverse correlation between p53 protein overexpression in the epithelium and MSI in the stroma was found (P=0.02475). The results suggest an alternative pathway of carcinogenesis involving stromal genetic instability in the development of colorectal cancers.

Phospholipid alterations in hepatocyte membranes and transporter protein changes in cholestatic rat model.

Biliary components are transported by hepatic adenosine triphosphate-binding cassette (ABC) transporters that are located in canalicular membranes. Physiological transporter function is related to membrane fluidity, which is modulated by the phospholipid composition of the lipid bilayer. We hypothesized that cholestasis may alter transporter function by modifying phospholipid species to protect the cell from cholestatic damage. Therefore, we examined the expression of ABC transport proteins and their mRNA levels in canalicular membrane vesicles isolated from rat liver 6 hr or three days after bile duct ligation. Membrane lipid composition and membrane fluidity of both sinusoidal and canalicular membrane vesicles were also examined. By 6 hr after bile duct ligation, we found a clear increase of mdr2 and bsep mRNA. These changes were associated with an increase of mdr-Pgp and with a clear decrease of mrp2 protein, and small decrease of bsep protein. In addition, mdrlb mRNA showed a strong increase by three days after bile duct ligation. Canalicular membrane fluidity decreased in a marked time-dependent manner, whereas sinusoidal membranes showed biphasic changes: increased fluidity at 6 hr and a decrease at three days. These changes were closely related to the changes of membrane lipid constitution; the saturated/unsaturated fatty acid ratio increased for phosphatidylcholine in canalicular membrane and the reverse occurred in sinusoidal membrane, and those for sphingomyelin showed the opposite pattern. We conclude that cholestasis causes modulation of ABC transporters as well as that of the lipid constitution in lipid bilayer. These may confer cytoprotective resistance to hepatocytes against cholestatic stress.

Dose-dependent conjugation of sulfobromophthalein and hepatic transit time in bile fistula rats: role of the microtubule-dependent vesicle pathway.

Sulfobromophthalein (BSP) is selectively taken up by the liver and secreted into the bile as unconjugated and conjugated forms. Our previous study demonstrated that unconjugated BSP, but not conjugated BSP, caused the dissociation of biliary lipid secretion from that of bile acids, suggesting that the hepatic BSP conjugation rate partly regulated biliary lipid secretion. To evaluate the mechanisms through which biliary lipid secretion is regulated by exogenous organic anions, we intravenously administered BSP to male Sprague-Dawley rats at various doses either continuously or as a bolus. Then the relationship of the dose of BSP to its conjugation rate, hepatic transit time, and biliary lipid secretion was determined. BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile acid secretion. In contrast, the proportion of conjugated BSP in bile was associated with the dose. Although the serum clearance of BSP after bolus infusion was constant regardless of the dose administered (50 or 200 nmol/100 g), BSP secretion was delayed with increasing doses: unconjugated BSP was secreted predominantly in the early phase (0-15 min after bolus injection), and conjugated BSP was the predominant form in the late phase (15-30 min). Pretreatment with colchicine reduced the conjugation rate and hepatic transit time of BSP, suggesting that the microtubule-dependent vesicle pathway plays a role in biliary excretion and conjugation of BSP. We conclude that biliary lipid secretion is influenced by organic anions with an affinity for bile acids such as BSP and that this effect is dependent upon the hepatic metabolic rate, i.e., conjugation rate. The hepatic transit time also plays a key role in this process by influencing metabolism.

[Relationship between prothrombin time international normalized ratio and thrombo test (%)].

OBJECTIVES: The optimal therapeutic range for laboratory evaluation of oral anticoagulant therapy is now defined by the prothrombin time international normalized ratio (PT-INR). However, the thrombo test (TT), an alternative method to measure intensity of anticoagulation, is also currently used throughout Japan. The relationship between PT-INR and TT (%) has yet to be clarified. This study investigated the relationship between PT-INR and TT (%). METHODS: The PT-INR and TT (%) were simultaneously measured of 505 consecutive samples from patients treated with warfarin in our hospital. Fourteen functions were used for regression analyses: a fractional function (Y = a/X + b), a square root function (Y = aX0.5 + b), a natural logarithmic function (Y = a.lnX + b), a power series function (Y = aXb), a quotient function (Y = abX), and polynomial functions [Y = anXn + an - 1Xn - 1 +......+ a1X1 + b, (1 < or = n < or = 9)]. The results were confirmed by the same methods in 383 samples and 296 samples from another two laboratories. RESULTS: The power series function showed the most significant (p < 0.0001) and highest adjusted R2 (0.858) correlation, with a regression formula of TT (%) = e4.48 (PT-INR)-2.09 in our laboratory. Using the same analyses, the power series function also showed the most significant and highest adjusted R2 in samples from the other two laboratories. CONCLUSIONS: This study showed that a power series function is the most appropriate for expressing the relationship between PT-INR and TT (%) among the 14 functions. The function between PT-INR and TT (%) is mainly derived from the relationship between TT (%) and TT (sec). Both internal validity and external validity confirmed the relationship between PT-INR and TT (%).

Involvement of agouti-related protein, an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action.

To understand the role of agouti-related protein (AGRP), an endogenous antagonist of hypothalamic melanocortin receptor, in leptin action, we produced a full-length recombinant AGRP and examined its effect on the satiety effect of leptin. We also studied leptin's regulation of hypothalamic AGRP mRNA expression. A single intracerebroventricular (i.c.v.) injection of AGRP significantly increased cumulative food intake and body weight in a dose-dependent manner in rats. The leptin-induced inhibition of food intake and body weight was reversed by co-injection of AGRP in a dose-dependent manner. Hypothalamic AGRP mRNA expression was upregulated in leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice and downregulated in lethal yellow agouti mice (KKAy mice) with hyperleptinemia. A single i.c.v. injection of leptin reversed the increased AGRP mRNA levels in ob/ob mice but not in db/db mice. In control mice and KKAy mice, AGRP mRNA expression was upregulated during fasting, when plasma leptin concentrations were decreased. No significant increase in AGRP mRNA expression was noted during fasting in control mice and KKAy mice treated with leptin. This study provides the first direct evidence that AGRP is a negative regulator of leptin action, and leptin downregulates hypothalamic AGRP production. Because leptin is shown to increase hypothalamic alpha-melanocyte stimulating hormone (alpha-MSH) production, our data suggest that its action via the hypothalamic melanocortin system is determined by the balance between the levels of its agonist and antagonist, alpha-MSH and AGRP.

Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion.

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. We have demonstrated that the hypothalamic arcuate nucleus (Arc) is a primary site of the satiety effect of leptin (Neurosci Lett 224:149-152, 1997). To explore the hypothalamic pathway of sympathetic activation of leptin, we examined the effects of a single intravenous or intracerebroventricular injection of recombinant human leptin on catecholamine secretion in rats. We also examined the effects of direct microinjection of leptin into the ventromedial hypothalamus (VMH), Arc, paraventricular nucleus (PVN), and dorsomedial hypothalamus (DMH) in rats. To further assess whether sympathetic activation of leptin is mediated via the VMH, we also examined the effects of a single intravenous injection of leptin in VMH-lesioned rats. A single injection of leptin (0.25-1.0 mg i.v./rat or 0.5-2.0 pg i.c.v./rat) increased plasma norepinephrine (NE) and epinephrine (EPI) concentrations in a dose-dependent manner. Plasma NE and EPI concentrations were increased significantly when leptin was injected directly into the VMH but were unchanged when injected into the Arc, PVN, and DMH. Plasma NE and EPI concentrations were unchanged in VMH-lesioned rats that received a single intravenous injection of leptin. The present study provides evidence that a leptin-induced increase in catecholamine secretion is mediated primarily via the VMH and suggests the presence of distinct hypothalamic pathways mediating the satiety effect and sympathetic activation of leptin.

Eicosapentaenoic acid release from the red alga Pachymeniopsis lanceolata by enzymatic degradation.

Forty-eight species of seaweeds from Japanese waters were screened for the valuable polyunsaturated fatty acids eicosapentaenoic acid (EPA). The eight species that contained the highest levels of these compounds were analyzed in detail. Of all species tested the red alga Pachymeniopsis lanceolata contained the highest EPA concentration, and it was present as both the free and bound forms. EPA constituted 38.7% of total fatty acids, and polar lipids were the main constituent of the total lipids in P. lanceolata. EPA was obtained from the marine algae P. lanceolata by enzymatic hydrolysis of the total lipids extract using phospholipase A2 (PLA2). The release of EPA reached a plateau after 10 min of enzymatic treatment. These results suggest that P. lanceolata is a useful natural source of EPA and that PLA2 treatment is a convenient method for obtaining EPA from the red alga.

Effect of trazodone in a single dose before bedtime for sleep disorders accompanied by a depressive state: dose-finding study with no concomitant use of hypnotic agent.

This was the first dose-finding study of trazodone that was designed to be free of the concomitant use of hypnotics, in which the drug was administered in a single dose for sleep disorders combined with a depressive state. As a result, trazodone at the dosage of 50-100 mg/day improved sleep disorders, particularly at the 100 mg/day dosage. It was confirmed that trazodone improved sleep disorders combined with a depressive state when it was administered in a single dose before bedtime with no concomitant hypnotics.

Comparison of thrombolytic therapies with mutant tPA (lanoteplase/SUN9216) and recombinant tPA (alteplase) for acute myocardial infarction.

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.

Structure-function studies of human leptin.

To elucidate the structural requirement of human leptin for its functions, the wild-type, mutant-type, C-terminal deletion, and N-terminal deletion were expressed in Escherichia coli and purified in soluble forms. These leptin analogs were intracerebroventrically injected into C57BL/6J ob/ob mice, and their in vivo biological activities were evaluated. The mutant-type leptin lacking a C-terminal disulfide bond reduced food intake at doses of more than 15 pmol/mouse, which was as effective as the wild-type leptin. C-terminal deletion without the loop structure, also significantly, but to a lesser extent, reduced food intake at doses of more than 90 pmol/mouse. However, N-terminal deletions showed no effect on food intake. We also evaluated the effects of the leptin analogs on radiolabeled leptin binding to its receptor in the choroid plexus using autoradiography. An excess of unlabeled mutant-type leptin as well as wild-type leptin led to complete inhibition of binding. C-terminal deletions led to weak inhibitory activity, whereas N-terminal deletions caused no inhibitory activity. These results clearly demonstrate that the N-terminal region of leptin is essential for both its biological and receptor binding activities. The amino acid sequence of the C-terminal loop structure is also important for enhancing these actions, whereas the C-terminal disulfide bond is not needed.

Development of a sensitive ELISA for human leptin, using monoclonal antibodies.

A new, sensitive ELISA for human leptin in plasma and cerebrospinal fluid (CSF) was developed, using monoclonal antibodies. The lower limit of detection of this ELISA was 0.78 pg/assay. Both intra- and interassay imprecision values were <7%. The dilution curves of plasma and CSF showed good linearity, and the recovery was 83.2-95.6%. There was good correlation between plasma leptin concentrations by the ELISA and a commercially available RIA (r = 0.99). Our ELISA is advantageous because it does not require radioisotopes, it produces results in hours rather than days, and more importantly, it improves on the detection limit and plasma interference of the RIA kit. The new ELISA enables measurement of low concentrations of leptin, as are seen in CSF and in plasma of patients with anorexia nervosa.

Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system.

Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.

A psychobehavioral factor, alexithymia, is related to coronary spasm.

The aim of this study was to assess whether the psychobehavioral pattern alexithymia is related to coronary artery spasm. Alexithymia, deficient psychological awareness, was examined using the Minnesota Multiphasic Personality Inventory Alexithymia Scale in 100 patients with angina pectoris in whom coronary spasm, defined as > or = 99% coronary narrowing, was documented upon ergonovine provocation, and in 109 patients with chest pain syndrome who were shown to have almost normal coronaries without inducible coronary spasm on coronary angiogram (control group). Alexithymia was approximately twice as prevalent in the coronary spasm group (31%) as in the control group (14%) (p<0.01). Among various conventional risk factors including hyperlipidemia, obesity, diabetes mellitus, hypertension, hyperuricemia, or family history of ischemic heart disease, only male sex and smoking were more prevalent in the coronary spasm group than in the control group (p<0.001). The odds ratios of coronary spasm adjusted for all the other risk parameters including sex and age were 4.14 [95% confidence interval (CI) 1.81-9.47] for alexithymia and 2.38 (95, CI 1.18-4.82) for smoking. A psychobehavioral pattern, alexithymia, relates to coronary spasm. This relationship is independent of the conventional coronary risk factors.