Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

OBJECTIVE: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. DESIGN: Longitudinal study. SETTING: University and foundation hospitals. SUBJECTS: Ten obese men and 10 premenopausal obese women. INTERVENTIONS: Five men and five women took 800 kcal/day LCD and another five men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. RESULTS: Plasma leptin levels in the LCD group decreased more markedly (46.2+/-14.6 to 13.2+/-3.6 ng/ml) than that expected for the decrement in percentage fat (39.0+/-1.7 to 35.9+/-1.7%) and body mass index (BMI; 35.4+/-2.4 to 33.1+/-2.2 kg/m(2)), while that in the BDD group did not decrease significantly (14.9+/-3.5 to 13.4+/-2.8 ng/ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5+/-2.7 vs 29.3+/-2.1%, P=0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r=0.586, P=0.0003) and T3 (r=0.785, P=0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r=0.928, P<0.0001). The plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter. CONCLUSIONS: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity. SPONSORSHIP: The Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labour and Welfare of Japan.     

Uptake of cadmium in meals from the digestive tract of young non-smoking Japanese female volunteers

OBJECTIVES: To estimate rates of cadmium (Cd) uptake from the digestive tract and changes in Cd in biological specimens after intake of Cd mainly in rice. METHODS: Twenty-five young non-smoking Japanese female volunteers (20-23 in age) were recruited and a 20-d experimental study was conducted. With polished rice containing 0.004 ppm and 0.340 ppm of Cd, Meal L and Meal H were prepared. Approximately 12% of total Cd in Meal L and 92% of total Cd in Meal H originated in rice. The volunteers ate Meal L for 11 d to achieve a stable intake-output balance of Cd. Fifteen of the 25 volunteers ate Meal H on the 12(th) day (Group D1), and the remaining 10 ate Meal H on the 12(th), 13(th) and 14(th) day (Group D3). All 25 subjects then resumed the consumption of Meal L to the end of the study (20(th) day). All meals, feces and urine were collected during the study, and Cd intake from the daily meals (Cd-I), Cd in feces (Cd-F) and Cd in urine (Cd-U) were determined. For measurement of Cd in blood (Cd-B), venous blood was collected from all volunteers on the day before the study and again on the 12(th) and 20(th) day; venous blood was also collected from 4-8 volunteers at additional time points. RESULTS: Mean Cd-I was 4.51 microg/d (range: 1.85-6.93) or 48.48 microg/d (range: 27.98-56.27) when they ate Meal L or Meal H. Cd-F and Cd-B exhibited faster responses to the change in Cd-I than did Cd-U. The Cd(uptake) rate, defined as (1-Cd-F(excess) /Cd-I(excess)) (Fig. 1), was 47.2% (range: -9.4-83.3%) in Group D1 and 36.6% (range: -9.2-73.5%) in Group D3, and the Cd(balance) rate, defined as (1-Cd-F(output) /Cd-I(intake)), was 23.9% (range: -4.0-37.7%) in Group D1 and 23.7% (range: -8.2-56.9%) in Group D3. CONCLUSIONS: Cd-F and Cd-B are better biological monitoring parameters for assessing change in Cd-I than Cd-U. The Cd(uptake) and Cd(balance) rates appeared to be higher than those in previous papers when ingested Cd mainly originated in rice.     

Increased plasma ghrelin level in lung cancer cachexia.

PURPOSE: Ghrelin, a novel growth hormone-releasing peptide,has been shown to cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in cachexia associated with lung cancer. EXPERIMENTAL DESIGN: Plasma ghrelin level was measured in 43 patients with lung cancer and 21 control subjects. Patients with lung cancer were divided into two groups: patients with cachexia (n = 21) and those without cachexia (n = 22). RESULTS: Plasma ghrelin level did not significantly differ between all patients with lung cancer and controls (157 +/- 10 versus 132 +/- 8 fmol/ml, P = 0.1). However, plasma ghrelin level was significantly higher in patients with cachexia than in those without cachexia (180 +/- 17 versus 135 +/- 10 fmol/ml, P = 0.011). Furthermore, plasma ghrelin level increased significantly in patients with decreased food intake after chemotherapy (from 136 +/- 11 fmol/ml to 170 +/- 16 fmol/ml on day 8, 179 +/- 20 fmol/ml on day 21 after start of chemotherapy), although plasma ghrelin level did not significantly change in those without decreased food intake. CONCLUSIONS: Baseline plasma ghrelin level was elevated in cachectic patients with lung cancer, and follow-up plasma ghrelin level increased in patients with anorexia after chemotherapy. Considering the positive energy effects induced by ghrelin, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with lung cancer.     

Successful treatment with chemotherapy of vinorelbine and gemcitabine for an elderly patient with advanced non-small cell lung cancer

A 74-year-old man with non-small cell lung cancer was referred to our hospital for chemotherapy. On admission, he suffered from high fever and left upper back pain. Laboratory data showed marked leukocytosis and increased CRP. He was treated with chemotherapy of weekly vinorelbine and gemcitabine. After the second cycle, the levels of leukocytes and CRP were remarkably decreased, and the severe back pain was also alleviated. He has been given an additional 4 cycles as an outpatient. He is now doing well. This regimen seems to be effective in alleviating symptoms and improving QOL.     

Pulpal response to a new light-cured composite placed in etched glass-ionomer lined cavities.

This study evaluated the pulp biocompatability of a new light-cured composite resin which was placed in etched glass-ionomer-lined cavities of monkey teeth. The pulpal response to this material was less than that to zinc-oxide eugenol cement in each observation period. Therefore this material seems to meet acceptable biocompatability standards in nonhuman primates.     

Morphological study of melt-crystallized linear low-density polyethylene by transmission electron microscopy

The morphology of the lamellae in non-isothermally crystallized linear low-density polyethylene (LLDPE), conventional high-pressure low-density polyethylene (HP-LDPE), and a high-density polyethylene (HDPE) sample was investigated by transmission electron microscopy (TEM). LLDPE exhibits clearly two different types of lamellae, i.e., thick, long, and straight lamellae like those of HDPE, and thin, short, and curved lamellae which grow among the former ones. Also LLDPE shows the broadest distribution of the values for the lamella thickness among the three types of polyethylenes mentioned. The average lamella thickness decreases in the order HDPE > LLDPE > HP-LDPE. Fractions were used to study the effects of the kind and the degree of short chain branching (SCB) and of the molecular weight in the range from 4100 to 3,1·10⁵. SCB has a predominant influence on the lamella thickness as well as on the shape, while the molecular weight does not largely affect lamella thickness but affects the shape of the lamellae. Further it was revealed from TEM observation that the isobutyl branch decreases lamella thickness more effectively than does the ethyl branch. This is in accordance with results from small-angle X-ray and differential scanning calorimetry measurements.     

Establishment and characterization of a new spontaneous metastasis model of human gastric carcinoma in nude mice.

A poorly differentiated medullary carcinoma of human stomach, designated HY-1, was successfully transplanted to nude mice by either the subcutaneous or intramuscular route for five generations. The transplanted tumor showed spontaneous lung metastases in nearly 100% of KSN and Balb/c female nude mice. There were over 20 visible lung metastatic nodules in KSN and Balb/c nude mice bearing tumors for over 80 days. Immunostaining of type IV collagen and electron microscopy revealed that tumor cells were often in direct contact with basement membrane (BM) of tumor blood vessels in the primary tumor tissue. At the site of contact between tumor cells and vascular BM, focal disappearance of the BM, disruption of endothelial cells and entry of tumor cell clusters into vascular lumen were observed. Immunostaining of 72 kDa gelatinase/type IV collagenase demonstrated that tumor cells expressed this enzyme in their cytoplasm. These results suggest that spontaneous metastasis of this tumor may be partly due to a marked tendency to vascular invasion involving the following sequential events: tumor cell contact with vascular BM, BM degradation possibly by 72 kDa gelatinases and endothelial disruption. This model could be a useful tool for understanding the mechanism of hematogenous metastasis of human gastric cancer.     

The Human Heart: A Self‐Renewing Organ

The dogma that the heart is a static organ which contains an irreplaceable population of cardiomyocytes prevailed in the cardiovascular field for the last several decades. However, the recent identification of progenitor cells that give rise to differentiated myocytes has prompted a re‐interpretation of cardiac biology. The heart cannot be viewed any longer as a postmitotic organ characterized by a predetermined number of myocytes that is defined at birth and is preserved throughout life. The myocardium constitutes a dynamic entity in which new young parenchymal cells are formed to substitute old damaged dying myocytes. The regenerative ability of the heart was initially documented with a classic morphometric approach and more recently with the demonstration that DNA synthesis, mitosis, and cytokinesis take place in the newly formed myocytes of the normal and pathologic heart. Importantly, replicating myocytes correspond to the differentiated progeny of cardiac stem cells. These findings point to the possibility of novel therapeutic strategies for the diseased heart.