Indium chloride bone marrow scintigraphy for hepatic myelolipoma: A case report.

BACKGROUND: As hepatic myelolipoma is rarely encountered, its radiological diagnosis using ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) is challenging. Hepatic myelolipoma is similar to fat-contained hepatic lesions seen in hepatocellular carcinoma and angiomyolipoma. Therefore, further development of techniques to diagnose hepatic myelolipoma is warranted. CASE SUMMARY: A 44-year-old obese man was found to have a hepatic lesion during his medical checkup. The lesion was 50 mm × 57 mm in size and was detected in segment 8 (S8) of the liver by US. The patient was diagnosed with hepatic lesion 20 years ago, but it was left unresolved. The patient had no symptoms, liver dysfunction, hepatitis virus antibody, or tumor marker elevation. Plain CT showed a well-defined lesion in S8 of the liver. The central and peripheral areas of the lesion primarily exhibited fat density and hypodensity, respectively. MRI revealed a capsule-like structure. Biopsy was performed to address the probability of hepatocellular carcinoma. The lesion was pathologically confirmed as a myelolipoma. Bone marrow scintigraphy performed using 111InCl3 revealed accumulation of the radiopharmaceutical in the soft tissue component, except in the fat-dominant part of the tumor, as well as in the surrounding liver parenchyma due to the presence of reticuloendothelial cells in the liver. CONCLUSION: This is the first report on the diagnosis of hepatic myelolipoma using 111InCl3 scintigraphy. The effectiveness of bone marrow scintigraphy for diagnosing hepatic myelolipoma might be limited. As radiopharmaceuticals accumulate in both hematopoietic and reticuloendothelial cells, the accumulation of radiopharmaceuticals in the lesion is obscure.

Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration.

In mammals, organ induction occurs only during embryonic development except for hair follicles (HFs). However, HF-resident epithelial stem cells (HFSCs), which are responsible for repetitive HF regeneration, are not fully characterized. Here, we establish in vitro culture systems that are capable of controlling the ability of HFSCs to regenerate HFs. Based on a method that precisely controlled the number of HFs for regeneration, functional analysis revealed that CD34/CD49f/integrin ß5 (Itgß5)-triple-positive (CD34+/CD49f+/Itgß5+) cells have multipotency and functional significance for continual hair regeneration. In native HFs, these cells reside in the uppermost area of the bulge region, which is surrounded by tenascin in mice and humans. This study unveils the subpopulation of HFSCs responsible for long-term hair cycling of HFs regenerated from bioengineered HF germ, suggesting the presence of functional heterogeneity among bulge HFSCs and the utility of our culture system to achieve HF regenerative therapy.

Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

Male-pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence-based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term "female-pattern hair loss (FPHL)" is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first-line treatments. Self-hair transplantation, irradiation by light-emitting diodes and low-level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t-flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan.

Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.

The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis. The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches. Potential applications of the 3D integumentary organ system include an in vitro assay system, an animal model alternative, and a bioengineered organ replacement therapy.

Cerebral regional cortical blood flow response during joint stimulation in cats.

Noxious stimulation of an elbow joint in the anesthetized cat increases cerebral blood flow over broad, bilateral areas of the cerebral cortex and increases systemic blood pressure. In order to eliminate the confounding effects of elevated blood pressure on cerebral blood flow, we re-examined this phenomenon in cats with a transected spinal cord at the T1 level. Noxious stimulation of an elbow joint resulted in a significant increase in blood flow in the forelimb area of the contralateral primary somatosensory cortex; the blood pressure remained unchanged. These data in cats suggest that the previously described bilateral increase in cerebral blood flow following noxious joint stimulation was due, in part, to the increased blood pressure.

Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats.

BACKGROUND: : Voglibose is an alpha-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug. METHOD: : In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0mg/100g of voglibose. Three weeks later, the rats were challenged with either 0.50g/kg CCl(4) orally or 0.75g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study. RESULTS: : Voglibose at these three experimental doses potentiated CCl(4) and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl(4) or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P450 3A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose. CONCLUSION: : Our study demonstrated that voglibose can potentiate CCl(4) and APAP hepatotoxicity in rats by inducing hepatic CYP2E1.

The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.

The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.

Testing potential effect of environmental endocrine disruptors in cow milk on reproductive index in female rats.

OBJECTIVE: To study the effect of endocrine disruptor chemicals in cow milk on female reproductive system. METHODS: A two-generation reproduction was conducted according to U. S. FDA standard. Milk was fed in special bottle to Wistar rats of both sexes through two successive generations (F0 and F1) in the milk group while artificial milk was fed to rats in the control group. Twenty-four rats of each sex were mated in each group. Measurements were made according to this guideline. RESULTS: Reproductive parameters in the milk group such as fertility index, gestation index, weights of uterus and ovary, days of vaginal opening, estrous cycles, histological morphological changes were comparable to those in the control group. However, the means of body weight had some differences. The body weight gains increased significantly in the milk-treated group in F1 and F2 generation compared with those in the control group. The concentration of insulin-like growth factor-1 (IGF-1) in blood in the milk group was comparable to that in the control group, but the standard deviation changed greatly in the milk-treated rats. CONCLUSION: Endocrine disruptor chemicals in milk have no severe effects on the female reproductive system.

Five-year efficacy of finasteride in 801 Japanese men with androgenetic alopecia.

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long-term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood-Hamilton scale. After separating patients into "sufficient" and "insufficient" efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood-Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.

Long-term effects of high dietary fiber intake on glucose tolerance and lipid metabolism in GK rats: comparison among barley, rice, and cornstarch.

Whether the intake of high dietary fiber may improve glycemic control in individuals with type 2 diabetes has been controversial. This study was conducted to observe the long-term effects of dietary fiber intake on glucose tolerance and lipid metabolism in rats. Thirty male type 2 diabetic model GK rats were divided randomly into 3 groups. Each group was fed either a barley (high-dietary fiber) diet, rice (low-dietary fiber) diet, or cornstarch (very-low-dietary fiber) diet. The rats were pair-fed for 9 months. The intake of the barley diet significantly improved the area under the plasma glucose concentration time curves, lowered the fasting plasma glucose and glycosylated hemoglobin levels, and decreased plasma total cholesterol (T Chol), triglycerides (TG), and free fatty acid (FFA) levels. This study demonstrated that long-term intake of barley has beneficial effects on glucose tolerance and lipid metabolism and suggests the intake of unrefined cereal foods should increase as a diet therapy for type 2 diabetes.

A two-generation reproduction study to assess the effects of cows' milk on reproductive development in male and female rats.

OBJECTIVE: To examine whether the considerable quantities of increased female sex hormone levels found in modern milk as a result of modern dairy farming practices are safe for human consumption. DESIGN: Males and females of the P generation were maintained on a diet containing milk for 10 weeks before mating. Exposure to milk was continued up to the end of weaning of the F2b offspring. SETTING: Two-generation reproduction study. ANIMAL(S): Male and female Wistar Galas rats. INTERVENTION(S): P- and F1-generation rats were mated. MAIN OUTCOME MEASURE(S): Fertility, fecundity, and morphology and function of reproductive organs. RESULT(S): Although milk had growth-promoting effects in both parents and offspring, it caused no impairments in fertility, fecundity, or reproductive organ development in either generation. However, a whole litter from a dam of the P generation was born dead, three litters in total had a pup with skeletal abnormalities, and the AGD of F2a female pups was reduced. These events occurred only in the milk-treated rats. It is unknown whether these issues had any relevance to milk or only happened by chance. CONCLUSION(S): Further study is required to determine whether milk from pregnant cows is completely free from adverse effects on reproductive health.

Activation of the intracerebral cholinergic nerve fibers originating in the basal forebrain increases regional cerebral blood flow in the rat's cortex and hippocampus.

In the rat, activation of the intracerebral cholinergic system originating in the basal forebrain and projecting to the cortex and hippocampus releases acetylcholine in the cortex and hippocampus, which results in vasodilation and an increase in regional cerebral blood flow (rCBF) in the cortex and hippocampus. The augmentation of rCBF is independent of both systemic blood pressure and regional metabolism. The intracerebral cholinergic fibers are able to act as autonomic nerve fibers for the regulation of cortical and hippocampal blood flow.

Decreased carbohydrate intake is more important than increased fat intake in the glucose intolerance by a low-carbohydrate/high-fat diet.

A low-carbohydrate/high-fat evening meal impaired the glucose tolerance of healthy subjects to almost the same extent as the impairment caused by overnight fasting. This suggests that the decreased component (carbohydrate) is more relevant than the increased component (fat) to the impairment of glucose tolerance by a low-carbohydrate/high-fat diet.

The effect of high carbohydrate diet on glucose tolerance in patients with type 2 diabetes mellitus.

The effect of high carbohydrate (hc) diet on glucose tolerance and on lipid profiles in patients with type 2 diabetes mellitus is contradicted. Japanese patients with mild type 2 diabetes mellitus were allocated either 55% standard carbohydrate (sc) or 80% high carbohydrate diets for 1 week, and OGTT and lipid profiles were examined. Then the diet was crossed over for another week, and OGTT and other identical parameters were re-evaluated. High carbohydrate diet improved the area under the glucose concentration-time curve (AUG) in 16/24 patients, and significantly increased and decreased 1,5-anhydroglucitol and homeostasis model assessment insulin resistance (HOMA-R) as a whole, respectively. Fasting plasma glucose (FPG) hc/sc ratio was inversely correlated with HOMA-R on a standard carbohydrate diet. High carbohydrate diet significantly decreased LDL- and HDL-cholesterol, whereas it significantly increased triglyceride. Furthermore, hc/sc ratios of the lipid parameters were inversely correlated with the respective parameters on standard carbohydrate diet. The present study indicates that high carbohydrate diet improved glucose tolerance depending on patients and the improvement in FPG was predicted by HOMA-R on a standard carbohydrate diet. The effect of high carbohydrate diet on glucose tolerance and lipid profiles should be investigated through a long-term study in the future.

Effects of a 4-week 70% high carbohydrate/15% low fat diet on glucose tolerance and on lipid profiles.

In order to investigate the effect of high carbohydrate/low fat diet on glucose tolerance and on lipid profiles, we performed a 4-week crossover study. Japanese subjects (30 patients with type 2 diabetes mellitus, 15 subjects with impaired glucose tolerance and 8 subjects with normal glucose tolerance) were allocated either 55% standard carbohydrate/30% fat (sc) or 70% high carbohydrate/15% low fat (hc) diet for four weeks, and evaluated by OGTT and various parameters. Then, the diet was crossed over to another diet, and identical parameters were re-evaluated after four weeks. Area under the glucose concentration-time curve (AUG) or triglyceride did not show significant changes between the two diets. HDL-Cholesterol and body mass index decreased significantly by hc diet. Free fatty acids and homeostasis model assessment insulin resistance index showed a tendency to be decreased by hc diet. AUG hc/sc ratio was inversely correlated with AUG or free fatty acids on standard carbohydrate diet. In conclusion, the present 4-week high carbohydrate/low fat diet may be useful to reduce body weight and insulin resistance. The 4-week high carbohydrate/low fat diet did not affect glucose tolerance as a whole. Although the 4-week high carbohydrate/low fat diet decreased HDL-Chol, it did not increase triglyceride.

Troglitazone enhances the hepatotoxicity of acetaminophen by inducing CYP3A in rats.

Troglitazone (TRZ) is the first of a new group of oral antidiabetic drugs, the thiazolidinediones, and is proven to lower plasma glucose levels in patients with type 2 diabetes mellitus. However, the concern has been raised because of several reports, in which severe hepatic dysfunction leading to hepatic failure was demonstrated in a few patients receiving the drug. We studied the effects of TRZ on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, both of which exert their toxic effects through bioactivation associated with cytochrome P450 3A (CYP3A) and 2E1 (CYP2E1). Male standard (Wistar/ST) and type 2 diabetic model (GK/Jal) rats were kept on a powdered chow diet containing 0, 100, 500 mg/kg/rat of TRZ. Three weeks later, the rats were either sacrificed for an in vitro metabolism study or challenged with 0.50 g/kg CCl(4) p.o. or 0.75 g/kg APAP i.p.TRZ at 100 and 500 mg/kg/rat increased the CYP3A level as well as the testosterone 6beta-hydroxylation activities in liver microsomes, but did not affect CYP2E1. TRZ also enhanced APAP hepatotoxicity, as evidenced by significantly increased levels of alanine aminotransferase, aspartate aminotransferase and alpha-glutathione S-transferase in the plasma of rats, and by significantly low hepatic glutathione concentration. Our study demonstrated that high doses of TRZ can enhance hepatotoxicity of APAP in Wistar/ST and GK/Jal by inducing hepatic CYP3A.

Effects of fiber intake on the blood pressure, lipids, and heart rate in Goto Kakizaki rats.

OBJECTIVE: The prevalence of hypertension in individuals with diabetes mellitus is higher than that in individuals without diabetes mellitus. High fiber intake decreases blood glucose and lipids levels. This study investigated the effects of cereal fiber intake on systolic and diastolic blood pressures in a rat model of type 2 diabetes mellitus. METHODS: Thirty male Goto Kakizaki rats were randomly assigned to one of three groups. Each group was fed a barley diet, a white rice diet, or cornstarch diet. The rats were pair fed for 16 wk. Systolic and diastolic blood pressures were measured once every 4 wk by the photoelectric oscillometric tail-cuff method without anesthesia. RESULTS: The barley diet significantly decreased systolic blood pressure from week 12 and decreased the plasma levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol. There were significant positive correlations between plasma lipids levels and systolic blood pressure. CONCLUSIONS: High fiber intake has beneficial effects on systolic blood pressure and blood lipids levels and suggests that fiber intake should be increased in individuals who have diabetes mellitus to prevent complications.

Regulation of cerebral cortical blood flow by the basal forebrain cholinergic fibers and aging.

This article reviews the study of neural vasodilator mechanisms of the cerebral cortex by basal forebrain cholinergic nerve fibers and their age-related function in rats. During the last decade, we have demonstrated a neural regulatory system of cerebral blood flow in rats involving intracerebral cholinergic vasodilator nerve fibers originating in the basal forebrain and projecting to the cerebral cortex. Activation of these cholinergic vasodilator fibers results in the release of acetylcholine (ACh) within the cortex, activation of both nicotinic and muscarinic ACh receptors, and vasodilatation without coupling to glucose metabolic rates. This cholinergic vasodilator system has been shown to decline with age in rats mainly due to age-related declines of nicotinic ACh receptor activity. However, muscarinic ACh receptor activity and the release of ACh into the extracellular space in the cortex are well maintained during aging. The present age-related decline of the intracerebral cholinergic vasodilator system found in rats seems to affect cognitive function during aging, although this cholinergic vasodilator system has not yet been demonstrated in humans.

Estrogen: one of the risk factors in milk for prostate cancer.

Studies to elucidate the cause of prostate cancer have met with little success to date. Epidemiological studies suggested that milk consumption is probably as one of the risk factors for prostate cancer. The studies thus focused on the fat and calcium in milk, but reached no definitive conclusion. According to the measurements of estrogen levels in milk by different studies, it was suggested that estrogen in milk was a possible risk to cause prostate cancer. One reason supporting this hypothesis is that Western diet (characterized by milk/dairy products and meat) causes a trend of increasing levels of estrogens, and Western males show a higher incidence rate of prostate cancer than Asia males. Estrogen levels in prostate fluid are also correlated very well with the prostate cancer. During several decades, estrogens, together with testosterone, was commonly used to induce the rodent model of prostate cancer. Our hypothesis also was supported by the presence of estrogen receptors in the prostate gland and the genotoxic role of estrogens on the prostate gland, as possible mechanisms. Therefore, if modern milk consumption does expose consumers to high levels of estrogen and plays an adverse role in prostate cancer, action should be taken to produce the noncontaminant milk.

[Effects of dietary fiber on the glucose tolerance in spontaneously diabetic rats--comparison among barley, rice, and corn starch].

OBJECTIVES: In this study, the effects of a barley diet containing high dietary fiber on the onset and development of diabetes mellitus in spontaneously diabetic rats was investigated by comparing with a rice diet containing low dietary fiber and an alpha-corn starch diet containing very low dietary fiber. METHODS: 30 male Goto-Kakizaki (GK) strain rats (8 weeks of age) were randomly assigned to 3 groups; high barley (HB) group on a barley diet (dietary fiber intake, 1.79 g/day/rat), rice (R) group on a rice diet (dietary fiber intake, 0.46 g/day/rat), and alpha-corn starch (CS) group on an alpha-corn starch diet (dietary fiber intake, 0.24 g/day/rat). The carbohydrate (70%), fat (10%), and protein (20%) contents of these 3 diets were equal, and the rats were pair-fed each diet for 3 months. RESULTS: Feeding for 3 months showed that fasting plasma glucose level in the HB group was significantly lower than in the R and CS groups; the glucose tolerance in the HB group was markedly improved. Moreover, the plasma cholesterol and triglyceride levels in the HB group were significantly lower than those of the R and CS groups. CONCLUSIONS: Our findings demonstrated that barley enabled glycemic control and improved glucose tolerance compared with rice or alpha-corn starch.