Oral Intake of Linseed Oil Inhibits Skin Barrier Dysfunction in Obese Mice.

OBJECTIVE: Obesity is not only a risk factor for lifestyle-related diseases but also causes skin barrier dysfunction, which leads to a reduced quality of life due to dryness, itching, and scratching, and thus requires appropriate treatment. However, there are no studies on this issue. Therefore, this study aimed to examine whether oral intake of linseed oil is effective for skin barrier function in obesity and to confirm how the effect is demonstrated. METHODS: TSOD mice received either sterile distilled water (Control group) or linseed oil (Omega group), containing a high level of omega-3 fatty acids, including α-linolenic acid, orally for eight weeks. Mice were then irradiated with ultraviolet B (UVB) and three days later, transepidermal water loss (TEWL), which is the primary outcome of skin barrier function, was measured and gross skin appearance was observed. Hematoxylin and eosin (HE) staining and Ki-67 immunostaining were performed on skin samples. mRNA expression levels of the inflammatory markers Tnfα, Cox2, Mcp1, and Hmox1 were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also performed fatty acid analysis of skin and erythrocytes by gas chromatography. Statistical analysis was performed using unpaired Student's t-test and Pearson's correlation analysis. RESULTS: Compared with the Control group, the Omega group exhibited lower TEWL values and little skin erythema. Histological analysis revealed thinner epidermis and fewer Ki-67 positive cells. Additionally, in the Omega group, mRNA levels of four inflammation-related genes were lower, α-linolenic acid levels in both skin and erythrocytes were higher, and a lower n-6/n-3 ratio was observed. And α-linolenic acid levels in the skin were negatively correlated with the expression levels of inflammation-related genes. CONCLUSION: Oral intake of linseed oil was found to inhibit skin barrier dysfunction in obesity. This effect was mediated by α-linolenic acid, a major component of linseed oil with anti-inflammatory properties, which was taken up by erythrocytes and supplied to the skin. Therefore, oral intake of linseed oil is expected to be a useful therapeutic method for skin barrier dysfunction in obesity.

Why and by How Much is Insulin Absorption Reduced by Insulin-derived Amyloidosis? A Scoping Review.

Insulin therapy is one of the central treatments for diabetes mellitus. Insulin-derived localized amyloidosis (IDLA) is a known skin-related complication of insulin injection. This is one of the causes of poor glycemic control in diabetic patients on insulin therapy. The aim of this study was to review and update the findings on the extent and mechanism of reduced insulin absorption in IDLA. A literature search was conducted on decreased insulin absorption and its mechanisms, and nine references were selected, with seven of these on decreased insulin absorption and four on mechanisms. Insulin absorption at IDLA sites was reported to be 27-94% lower compared with normal sites. In addition, a comparison between nonpalpable and palpable IDLA sites revealed a significant decrease in insulin absorption at the palpable IDLA site. The mechanism of insulin malabsorption was found to be a reduction in insulin absorption at the palpable IDLA sites. Four mechanisms of decreased insulin absorption were identified: decreased subcutaneous blood flow, adsorption of administered insulin onto insulin amyloid fibers, impaired diffusion of insulin subcutaneously, and physical factors such as shaking of the insulin preparation. These mechanisms should be investigated in vivo in the future.

Association Between Anxiety and Depressive Symptoms During Prehospitalization Waiting Period and Quality of Recovery at Postoperative Day 3 in Perioperative Cancer Patients.

PURPOSE: Perioperative depressive symptoms are associated with poor postoperative quality of life (QOL), leading to prolonged hospital stays, and delayed return to society. Previous studies show that physical and mental states change on the third day after surgery, and there is a correlation between quality of recovery (QoR) on this day and QOL at 3 months after surgery. QoR after surgery is an important indicator of postoperative QOL. However, there are no reports on the association between depressive symptoms, and postoperative QoR. Therefore, the study purpose was to clarify the relationship between depressive symptoms in perioperative cancer patients during the prehospitalization waiting period, and QoR on the third postoperative day. DESIGN: This was a prospective cohort study. METHODS: We examined whether depressive symptoms during the prehospitalization waiting period were related to QoR on day 3 after surgery in perioperative cancer patients. Subjects were patients with primary tumors who underwent surgery under general anesthesia. Subjects completed self-administered questionnaires during the prehospitalization waiting period and on postoperative day 3. The presence and/or absence of depressive symptoms was measured using the Hospital Anxiety and Depression Scale. Subjects were divided into two groups: depressive symptoms or non-depressive symptoms. Postoperative QoR was determined using the QoR-40 questionnaire and we calculated the rate of change in QoR-40 global and dimension scores from preoperation to postoperation. FINDINGS: 231 individuals met the inclusion criteria and agreed to participate in the study. Of these, 173 were included in the analysis. Only the rate of change in emotional state differed significantly between groups (P = .022). Both global and dimension QoR-40 scores were lower in the depressive symptoms group than in the non-depressive symptoms group. CONCLUSIONS: These findings demonstrate the need to provide both psychological and physical support continuously from the preoperative to early postoperative stage for cancer patients with depressive symptoms in the prehospitalization waiting period.

Reduced skin lipid content in obese Japanese women mediated by decreased expression of rate-limiting lipogenic enzymes.

Skin barrier function is often deficient in obese individuals, but the underlying molecular mechanisms remain unclear. This study investigated how skin structure and lipid metabolism, factors strongly associated with barrier function, differed among 50 Japanese women of greatly varying body mass index (BMI). Subjects receiving breast reconstruction surgery were chosen for analysis to obtain skin samples from the same site. The subjects were classified into two groups, control (BMI < 25 kg/m2) and obese (25 kg/m2 ≤ BMI < 35 kg/m2), according to standards in Japan. Hematoxylin and eosin staining was used to assess skin thickness, Ki-67 immunostaining to examine keratinocyte proliferation, and real-time polymerase chain reaction to measure skin expression levels of genes associated with lipid metabolism. Total lipids, cholesterol, and fatty acids were also measured from these same skin samples. In the obese group, structural changes included epidermal thickening and an increase in the number of Ki-67-positive (proliferating) cells. Both skin cholesterol and fatty acid levels exhibited an "inverted-U" relationship with BMI, suggesting that there is an optimal BMI for peak lipid content and barrier function. Decreased lipid levels at higher BMI were accompanied by downregulated expression of PPARδ and other genes related to lipid metabolism, including those encoding acetyl-CoA carboxylase and HMG-CoA reductase, the rate-limiting enzymes for fatty acid and cholesterol synthesis, respectively. Thus, elevated BMI may lead to deficient skin barrier function by suppressing local lipid synthesis.

Efficacy of Kaempferia parviflora in a mouse model of obesity-induced dermatopathy.

Obesity results from excessive energy intake and physical inactivity, and predisposes one to various diseases. One of these reasons is that enlargement of adipocytes raises the lipid metabolic abnormalities that affect various organs. The skin is one such organ, and it has been reported that subcutaneous adipocyte cells secrete various factors and these factors are involved in reduction of dermal collagen fibers and fragility of the skin in obesity. The present study explored the efficacy of Kaempferia parviflora (KP) in preventing obesity-induced dermatopathy. We used Tsumura Suzuki obese diabetes (TSOD) mice as an obesity model. TSOD mice were fed a standard diet (MF) mixed with either an ethanol extract from KP (KPE), polymethoxyflavonoid-rich extract from KP (PMF), or polymethoxyflavonoid-poor extract from KP (X). We then evaluated the effect of these three KP fractions on aging-like skin damage induced by UVB irradiation. KPE and PMF caused a significant decrease of mouse body weight, and suppressed the increase in the thickness of the subcutaneous fat layer. In addition, KPE shifted the frequency of subcutaneous adipocyte sizes towards smaller cells possibly via its polypharmacological actions. Scanning electron microscopy revealed that the stereostructure of the collagenous fibers in the dermis was better retained in the KPE and PMF groups, in that order. These results offer the first evidence that KPE can attenuate obesity-induced dermatopathy more effectively than PMF, suggesting that KPE (or KP) might be a candidate supplement for preventing obesity-related skin disorders.

Reduction and fragmentation of elastic fibers in the skin of obese mice is associated with altered mRNA expression levels of fibrillin-1 and neprilysin.

AIM OF THE STUDY: Our previous research suggested that obesity induces structural fragility in the skin. Elastic fibers impart strength and elasticity. In this study, we determined whether elastic fibers decrease in the skin of obese mice. MATERIALS AND METHODS: To confirm alterations in elastic fiber content due to obesity, we used spontaneously obese model mice (TSOD) and control mice (TSNO). Furthermore, to evaluate the elastin structure and gene expression dependent on the severity of obesity, an obesity-enhanced mouse model was developed by feeding a high fat diet to TSOD (TSOD-HF). Back skin samples were stained with hematoxylin and eosin and Elastica van Gieson for microscopic examination, and the samples were stained for immunohistochemical analysis of neprilysin. Gene expression levels were determined using a real-time PCR system. RESULTS: The abundance of elastic fibers beneath the epidermis was remarkably reduced and fragmented in TSOD as compared with TSNO. Fibrillin-1 mRNA levels in TSOD were significantly suppressed compared with those in TSNO, whereas neprilysin mRNA levels and immunohistochemical expression in TSOD were significantly increased, as compared with those in TSNO. The reduction of elastic fibers was enhanced and the expression levels of elastic fiber formed factors were significantly suppressed in TSOD-HF, as compared with those in the TSOD. CONCLUSIONS: The abundance of elastic fibers was reduced and fragmented in obesity, suggesting that the reduction in elastic fibers is initially caused by increased neprilysin and decreased fibrillin-1 expression, which may inhibit formation and stabilization of elastic fibers, resulting in skin fragility in obesity.

Association Between Components of Exudates and Periwound Moisture-Associated Dermatitis in Breast Cancer Patients With Malignant Fungating Wounds.

Excessive wound exudates are troublesome symptoms of malignant fungating wounds. In particular, such exudates may cause periwound moisture-associated dermatitis (MAD). In this study, we focused on factors that contribute to skin irritation by exudates in breast cancer patients with malignant fungating wounds. Our aim was to identify the relationship between MAD surrounding malignant fungating wounds and levels of various candidate irritating factors in their exudates. We recruited 20 breast cancer patients with exudates from malignant fungating wounds and collected three types of exudate samples: pooled exudate, swab, and fresh exudate samples. We measured the pH, concentrations of polyamines (putrescine [PUT], cadaverine [CAD], spermidine, and spermine), and matrix metalloproteinases (MMP2 and MMP9) in the exudates and cultured them for bacteria. Differences between participants with and without MAD were assessed using Fisher's exact test or the Mann-Whitney U test. Of the 20 participants, 14 had MAD. There were no significant differences in median pH and MMP activity between patients with and without MAD. The level of PUT was significantly higher in the MAD than in the non-MAD group (p = .008), and CAD was detected only in the MAD group (p = .016). Prospective studies are needed to clarify correlations and causal relationships between polyamines and erythema and identify therapeutic targets for preventing the development of MAD.

Impaired aquaporin 3 expression in reepithelialization of cutaneous wound healing in the diabetic rat.

Impaired cutaneous wound healing is a serious complication of diabetes mellitus (DM). Currently, little is known about reepithelialization in DM. However, recent studies identified aquaporin 3 (AQP3), a transmembrane protein that functions as a pore-like passive transporter, to be a key molecule in cutaneous epidermal wound healing. AQP3 expression is downregulated in response to tumor necrosis factor-alpha (TNF- α). Given that systemic TNF-α levels are functionally connected to impaired healing in diabetic mice and that both diabetic and Aqp3-deficient animals exhibit impaired reepithelialization, the authors hypothesized that impaired AQP3 expression might contribute to diabetes-impaired wound healing. In the present study, the authors examined AQP3 expression in the regenerating epidermis during cutaneous full thickness wound healing and in intact skin of a streptozotocin-induced diabetic rat model. Aqp3 messenger RNA expression levels were decreased in wounds of DM rats compared to controls. Immunohistochemical analysis showed an absence of AQP3 in the stratum spinosum of the regenerating epidermis in the DM group, whereas the stratum basale was positive for AQP3 in both groups. In summary, these findings suggest that there may be a relationship between impaired AQP3 expression and diabetes-delayed reepithelialization. Thus, future nursing studies should focus on this mechanism in diabetic wound healing.

Aging-like skin changes induced by ultraviolet irradiation in an animal model of metabolic syndrome.

Both physiological skin aging and pathologic photo-aging caused by ultraviolet (UV) irradiation are mediated by latent inflammation and oxidative stress. Although numerous animal skin-aging models have used UV irradiation, most require massive doses or long-term irradiation. To establish a more refined skin-aging model, we focused on an animal model of metabolic syndrome (MS) because MS involves damage to various organs via oxidative stress or inflammation, similar to the changes associated with aging. We hypothesized that MS skin might exhibit more aging-like changes after milder, shorter-term UV irradiation than would normal animal skin under similar conditions, thus providing a useful model for skin aging. The authors therefore examined the skin from Tsumura Suzuki obese diabetic (TSOD) mice (MS model) and control Tsumura Suzuki non-obese (TSNO) mice before and after UV irradiation. Skin from TSOD mice had a thinner epidermis and dermis, a thicker fatty layer, reduced density and convolution of the fragmented collagen fibers, and upregulated expression of tumor necrosis factor (TNF)-α, a dual marker for inflammation and aging, compared to the skin from TSNO mice. UV irradiation affected TSOD skin more severely than TSNO skin, resulting in various changes resembling those in aged human skin, including damage to the dermis and subcutaneous fatty tissue, infiltration of inflammatory cells, and further upregulation of TNF-α expression. These results suggest that UV-irradiated TSOD mice may provide a new model of skin aging and imply that skin from humans with MS is more susceptible to UV- or aging-related damage than normal human skin.

Preventive effects of Bofutsushosan on obesity and various metabolic disorders.

Visceral fat accumulation has been reported as the most important risk factor for the development of various metabolic disorders. In this study, the preventive effects of Bofutsushosan, a Japanese Kampo preparation, on obesity and various metabolic disorders were investigated focusing on visceral fat accumulation using Tsumura, Suzuki, Obese, Diabetes (TSOD) mice, which showed significant accumulation of visceral fat, and developed metabolic disorders including glucose intolerance, hyperlipidemia, hypertension and hyperinsulinemia. At 2 months after initiation of the study, the control TSOD mice developed various metabolic disorders such as marked obesity and visceral fat accumulation, increases in the levels of blood glucose, insulin, total-cholesterol (TC) and triglyceride (TG), and abnormal glucose tolerance, hypertension and peripheral neuropathy as distinct from the control Tsumura, Suzuki, Non-Obesity (TSNO) mice, which do not develop obesity and various metabolic disorders. In the TSOD mice treated with Bofutsushosan, body weight gain and visceral/subcutaneous fat accumulation were significantly suppressed. Biochemical parameters in plasma (glucose, TC, insulin and tumor necrosis factor-alpha (TNF-alpha) level) were significantly suppressed, and abnormal glucose tolerance, elevation of blood pressure and peripheral neuropathy accompanying progression of metabolic disorders were also significantly suppressed. On the other hand, in TSNO mice, Bofutsushosan showed no noteworthy impacts on most parameters except for an improvement of the lipid plasma level. The above results suggested that Bofutsushosan could be effective in preventing obesity and various metabolic disorders.

[Single center survey of the relationship between pregnancy anemia and prepregnancy lifestyle].

Physiologically, anemia often occurs during pregnancy because of an increase in circulating plasma volume. Pregnancy anemia is found prenatally in 50-75% of women. Based on the present survey performed in our obstetrics and gynecology ward, 52% of women experienced anemia during their pregnancy. This suggests that normal physiological changes due to pregnancy alone are not the only factors contributing to pregnancy anemia. Therefore to study the influence of lifestyle on pregnancy anemia, we investigated prepregnancy lifestyles on the assumption that the accumulation of several factors over a long period is usually the cause of anemia. The present results suggest that (i) the probability of anemia is slight in late pregnancy, if a normal Hb concentration is maintained in early pregnancy; (ii) the menstrual cycle is involved in the onset of anemia during early pregnancy; (iii) the number of meals taken and the level of alcohol consumption influence Hb concentration in late pregnancy. We believe that these findings provide a useful information source for advising patients on avoiding pregnancy anemia, which we can also use as guidance for outpatients at puberty. In conclusion, to prevent pregnancy anemia it is important to keep a regular menstrual cycle before pregnancy, and to take 3 meals/day and abstain from alcohol before and during pregnancy.

Efficacy of Tokishakuyakusan on the anemia in the iron-deficient pregnant rats.

Iron-deficiency anemia not only causes insufficient oxygen delivery to the body of the mother, but creates serious conditions in the fetus, such as insufficient oxygen delivery and poor development, and its treatment has become an important issue. To elucidate the mechanism of the anemia-ameliorating action of Tokishakuyakusan, we investigated the effect of administration of Tokishakuyakusan on anemia-related parameters and the serum transferrin and erythropoietin levels, erythrocyte morphology, and bone marrow cells in pregnant rats and in pregnant rats with iron-deficiency anemia. The results showed that Tokishakuyakusan significantly improved the low erythrocyte count, hemoglobin, and hematocrit values of the pregnant rats in the iron-deficient state, increased the proportion of normal erythrocytes in terms of erythrocyte morphology, increased the proportion of erythroblasts among bone marrow cells, and also significantly increased the erythropoietin and transferrin levels in the blood. These findings suggested that Tokishakuyakusan promotes erythrocyte differentiation in iron-deficiency anemia, and that it possesses anemia-ameliorating efficacy.

A comparative study of laboratory parameters and symptoms effected by Toki-shakuyaku-san and an iron preparation in rats with iron-deficiency anemia.

In order to more closely examine the effect of Toki-shakuyaku-san and an iron preparation in vivo in an animal experiment, we prepared anemic rats, divided them into 4 groups, i.e., an untreated group, a Toki-shakuyaku-san group, an iron-preparation group and a Toki-shakuyaku-san+iron-preparation group, and assessed the results of laboratory parameters, hematology, and general symptoms of anemia. The results showed trends toward improvement in indices of anemia, i.e., erythrocyte (RBC) count, hemoglobin (Hb), hematocrit (Ht) and serum iron (Fe), and improvement of anemic symptoms in the 3 treated groups. Examination of erythrocyte morphology showed that erythrocyte destruction had occurred only slightly in the 3 treated groups. The organ weight measurements showed an increase in the weight of the heart and spleen in the untreated group, but tended to be closer to normal in the 3 treated groups. The number and wet weight of the feces in the untreated group were markedly lower than normal, but increased in the Toki-shakuyaku-san group. In the iron-preparation group, the hemorrhage of stomach and pigmentation of the tail which seem to be a side effect of iron were observed, but was not seen in the Toki-shakuyaku-san group. The results animal experiment more closely examined the results of clinical study, and we concluded that by using Toki-shakuyaku-san and the iron preparation in combination, it is possible to lessen the adverse reactions such as gastrointestinal symptoms, and that more ameliorative effect on the anemic state can be expected.

A comparative study of the usefulness of toki-shakuyaku-san and an oral iron preparation in the treatment of hypochromic anemia in cases of uterine myoma.

We prospectively studied and compared the usefulness of Kampo medicine (Sino-Japanese traditional herbal medicine) "Toki-shakuyaku-san" and an oral iron preparation in the treatment of hypochromic anemia associated with uterine myoma. The study subjects consisted of 25 patients who were diagnosed as having hypochromic mild to moderate anemia associated with menorrhagia attributable to uterine myoma. They were divided into the Toki-shakuyaku-san group (n = 10) and the oral iron group (n = 15). We monitored the blood counts, subjective symptoms, and occurrence of side effects after oral administration of either preparation for 4 and 8 weeks in these subjects. In regard to the blood counts and improvements of the laboratory parameters of anemia, while marked improvement was observed in the oral iron group, no significant improvement was noted in the Toki-shakuyaku-san group. On the other hand, in terms of improvement of the signs and symptoms of anemia, such as facial pallor, spoon-shaped nails and dizziness, the latter group also showed significant improvement. In addition in the Toki-shakuyaku-san group, resolution of symptoms such as hypermenorrhea, dysmenorrhea, feeling cold, dizziness, headache and shoulder stiffness was also noted. While side effects were encountered in 80.0% of patients in the oral iron group, no significant side effects were observed in the Toki-shakuyaku-san group. From these findings, it is considered that Toki-shakuyaku-san may be useful for resolving the symptoms of mild or moderate anemia associated with uterine myoma.