Tomoi Sato

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.

Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia

In cancer anorexia, a decrease in food intake (FI) occurs concomitant with changes in orexigenic peptides such as neuropeptide Y (NPY) and anorexigenic peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) and anorexigenic neurotransmitter serotonin. omega-3 Fatty acid (omega-3FA) inhibits cytokine synthesis, and delays tumor appearance, tumor growth, and onset of anorexia in tumor-bearing rats. We hypothesize that, in cancer anorexia, omega-3FA is associated with quantitative reversal of hypothalamic NPY, alpha-MSH, and serotonin receptor (5-HT(1B)-receptor) enhancing FI. Fischer rats were divided into: MCA tumor bearing fed chow (TB-Chow) or omega-3FA diet (TB-omega-3FA) and controls: non-tumor bearing fed chow (NTB-Chow) or omega-3FA diet (NTB-omega-3FA). Rats were euthanized at anorexia and brains were removed for hypothalamic immunohistochemical study, using NPY, alpha-MSH, and 5-HT(1B)-receptor-specific antibodies and slides assessed by image analysis. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. At anorexia, FI decreased (P < 0.05) in TB-Chow but did not change in TB-omega-3FA rats. In TB-omega-3FA vs. TB-Chow, NPY immunoreactivity increased 38% in arcuate nucleus (ARC; P < 0.05), and 50% in magnocellular paraventricular nucleus (mPVN; P < 0.05). alpha-MSH decreased 64% in ARC and 29% in mPVN (P < 0.05). 5-HT(1B)-receptor immunoreactivity decreased 13% only in supraoptic nucleus (P < 0.05). No immunoreactivity was found in the control sections. omega-3FA modified hypothalamic peptides and 5-HT-(1B)-receptor immunoreactivity at anorexia, concomitant with an increase in FI, were probably mediated by omega-3FA inhibition of tumor-induced cytokines.

Hepato-vagal pathway associated with nicotine's anorectic effect in the rat.

Nicotine reduces appetite and body weight. Because the hepato-portal area senses different types of nutrients that transmit signals via vagal afferent nerves to the hypothalamus to modify food intake and feeding pattern, we investigated the effect of nicotine on a hepato-vagal-hypothalamic pathway. Low doses of nicotine (< 10 ng) injected into portal vein (i.p.v.) decreased, while high doses of nicotine increased (> or = 10 ng) electrophysiological activity of hepatic vagal afferents. Stimulatory effect of high dose of nicotine on vagal hepatic afferents was blocked by a prior i.p.v. injection of curare (30 microg) or hexamethonium (1 mg). Furthermore, activities of gastric vagal and adrenal sympathetic efferents were suppressed by low-dose, but stimulated by high-dose i.p.v. nicotine. These reflex effects did not occur in hepatic vagotomized rats. Results of experiments demonstrate that in addition to nicotines anorectic effect being mediated via a direct central action, nicotine also acts peripherally via hepatic vagal afferents from sensors of nicotine in the hepato-portal region.

Plasma Leptin, Insulin And Free Tryptophan Contribute To Cytokine-Induced Anorexia

Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

Diagnostic peritoneal lavage for diagnosing blunt hollow visceral injury: The accuracy of two different criteria and their combination

PurposeTo test the usefulness of diagnostic peritoneal lavage (DPL) for identifying blunt hollow visceral injury with two different sets of criteria or a combination of the two.MethodsFifty victims with physical examinations and/or computed tomography findings equivocal for blunt hollow visceral injury underwent DPL. Whether or not to perform surgery was determined based on Otomos DPL criteria [lavage white blood cell counts (L-WBC) over lavage red blood cell counts (L-RBC) divided by 150 (L-WBC ≥ L-RBC/150) in the presence of hemoperitoneum, or L-WBC over 500/mm3 (L-WBC ≥ 500) in the absence of hemoperitoneum]. The cell count ratio, a comparison of L-WBC, L-RBC, peripheral WBC (P-WBC), and peripheral RBC (P-RBC) [(L-WBC/L-RBC)/(P-WBC/P-RBC) ≥ 1] were all calculated retrospectively.ResultsThere were one and two false-positive cases based on Otomos criteria and the cell count ratio, respectively, with corresponding accuracies of 97.8% and 95.7%, respectively. There were no false-positive or -negative cases according to the combined use of Otomos criteria and cell count ratio, yielding an accuracy of 100%.ConclusionAlthough each criterion alone is very accurate in predicting the presence of blunt hollow visceral injury, the combined use of the two would further improve the accuracy of the diagnosis and thereby reduce the number of unnecessary celiotomies.

Spontaneous esophageal rupture successfully treated by conservative therapy: report of two cases.

Spontaneous esophageal rupture is a life-threatening condition for which surgical intervention within 24 h after the onset is usually recommended. This report describes two cases of spontaneous esophageal rupture successfully treated by conservative therapy. In the first case, a 68-year-old man was hospitalized for severe upper abdominal pain following hematemesis. A large left pleural effusion occurred the next day and spontaneous esophageal rupture was diagnosed 1 week later, following placement of an intrathoracic drain. In the second case, a 38-year-old man was admitted for severe back pain following vomiting and esophageal rupture diagnosed within 3 h after onset by computed tomography (CT), which showed left pleural effusion, pneumothorax, and pneumomediastinum. Both patients were successfully treated conservatively with continuous intrathoracic drainage, intravenous antibiotics, and hyperalimentation. We conclude that spontaneous esophageal rupture can be treated conservatively under intensive observation.

Intra-supraoptic nucleus sulpiride improves anorexia in tumor-bearing rats

Previous studies suggest that the dopaminergic system in the supraoptic nucleus (SON) is involved not only in the water balance control but also in the food intake regulation. Since we reported that an injection of the D2 receptor antagonist, sulpiride, into specific hypothalamic nuclei (e.g. the LHA, or the VMN) increases food intake in anorectic tumor-bearing rats, as well as in normal rats, we hypothesized that an injection of sulpiride into the SON would also improve cancer anorexia. Sulpiride injection (4 μg/0.5 μl) into bilateral SON of anorectic tumor-bearing male rats significantly improved food intake via increases in both meal size and meal number. These data suggest that pharmacological manipulation of the hypothalamic dopaminergic system is feasible in amelioration of cancer anorexia.

Feeding behavior during sialodacryoadenitis viral infection in rats.

Abstract Sialodacryoadenitis (SDA) is a highly contagious common viral infection in rats, akin to mumps in humans. Anorexia occurs during such viral infection. But the pattern of the decrease in food intake (a decrease in either meal size and meal number or both) during spontaneous viral infection has not been previously characterized. We observed the onset of anorexia and an abnormal feeding pattern during an opportunistic SDA viral infection in our rat colony. We thus studied seven male rats. Before the viral infection there was a positive association between food intake and meal number (P<.05). After infection food intake decreased by 68%. This occurred via a significant decrease in meal size (by 69%) (P<.05); and a nonsignificant decrease in meal number (P=.71). This pattern of decreased food intake is similar to that occurring during indomethacin-induced ulcerative ileitis, where we previously measured an increase in plasma tumor-necrosis factor (TNF)-α. Anorexia in response to bacterial lipopolysaccharide administration, which is also linked to plasma TNF-α, is however, caused only via a decrease in meal number. The differences in the decrease in the feeding pattern between the SDA viral and a bacterial infection suggest that factors other than TNF-α alone play a significant role in the mechanism of anorexia during a viral infection.

Ductal carcinoma in situ with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl

We report here a quite rare case of ductal carcinoma in situ (DCIS) with isolated tumor cells in the sentinel lymph node in a 17-year-old adolescent girl whose mother also had advanced breast cancer. Findings included an elastic mass in the right breast accompanied by serous nipple discharge. DCIS of the breast was diagnosed following core needle biopsy. Although no invasive focus was clearly observed in the mastectomy sample, isolated tumor cells were found in the sentinel lymph node. Although the family refused genetic testing, a hereditary abnormality may have played a role in the carcinogenesis in this case.

Invasive Paget’s disease of the male nipple: a case report

Abstract Male mammary Paget’s disease (MPD) is extremely rare. Furthermore, MPD with invasion downward into the dermis of the male nipple has been reported rarely. A 56-year-old Japanese man presented with a lump and eczema in the right nipple–areola area. Ultrasonography revealed only a cystic lesion below the right areola. With a diagnosis of MPD with invasion into the dermis associated with ductal carcinoma in situ, mastectomy and sentinel lymph node biopsy were performed. MPD with dermal invasion is extremely rare, and only one male case has been reported in the English literature; therefore, the current case is the second case of male MPD with dermal invasion.