Identification of Drugs and Patient Profiles at Risk for Severe Skin Injuries Due to Extravasation: Analysis of a Spontaneous Reporting System.

This study aimed to identify risk factors and combinations thereof that are associated with severe skin injuries due to the extravasation of injectable drugs. A cross-sectional study using the Japanese Adverse Drug Event Report database was conducted according to the RECORD-PE checklist. Adverse event reports related to necrosis, ulcers, or erosions due to extravasation were considered "with severe skin injury," and others were considered "without severe skin injury." Approximately 255 cases "with" and 260 cases "without" severe skin injury were identified. The relationship between the incidence of severe skin injury and age, sex, drugs, and primary disease was evaluated using the χ2 test. Association rule mining was used to evaluate the correlation between each combination of factors and skin injury. Nine factors were identified as independent risk factors for severe skin injury, including age (<10 or ≥70 years), peripheral parenteral nutrition use, and mental disorders. The association rule mining results suggested that a combination of specific patient backgrounds and drug use was associated with the incidence of necrosis or ulcers. The findings of this study reiterate that nurses might consider closely observing patients with the risk factors identified in this study for the prevention and early detection of extravasation-related skin injuries.

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.

mRNA expression levels of cytochrome P450 CYP1A2, CYP3A4, and CYP3A5 in the epidermis: a focus on individual differences among Japanese individuals.

Various cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood.To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated.There were considerable individual differences in epidermal CYP1A2 mRNA expression levels, and CYP1A2 showed a weak positive correlation with CYP3A4 mRNA expression levels. In contrast to previous results for other organs, epidermal CYP3A4 mRNA expression levels showed a weak positive correlation with BMI.CYP3A4 in the epidermis may have been locally enhanced as a defence mechanism against xenobiotics in response to impaired barrier function. These differences in mRNA expression in the skin may affect the transdermal absorption of drugs, such as lidocaine and fentanyl, which are metabolised by multiple overlapping CYPs.Our study provides new insights into drug metabolism in the skin. These results are valuable for predicting drug effects and transdermal drug transfer rates in Japanese patients.

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.

[Pharmacology education in nursing degree course in order to cultivate nurses skilled in drug therapy].

In nursing degree course education, it is needed to enhance contents of pharmacology education for acquiring nursing practice ability in the nursing education model core curriculum and revision of designation regulations. Therefore, it is intended to consider pharmacology education in nursing degree course in universities in the current study in order to cultivate nurses skilled in drug therapy. We have conducted a survey on knowledge required for students of universities of nursing as well as an analysis on contents of inquiries made by nurses on drugs. As a result, it has been revealed that students have recognized effect and side effects of drugs as basic knowledge required for a nurse. With less recognition required on pharmacokinetics and practical contents, however, the knowledge held by students was dissociated with practical knowledge often required for nurses when administering drugs. A possibility has been also revealed by the current survey that nurses may not be able to make use of pharmacokinetics as pharmacological knowledge for patients' treatment management. From results of the survey and previous study, it is believed to be necessary in university education to extend pharmacological knowledge from its basic to clinical stage and build up adequate basic knowledge and thinking power of pharmacology in nursing degree course as well as to sufficiently learn and understand necessity of pharmacokinetics for conducting evaluation of drug efficacy.

[Pharmacology education in nursing: what should be taught and how? - from Western to Chinese medicine].

Doctors give prescriptions after considering the medical conditions of patients. Pharmacists check the prescription and give information about the effects of the drugs to the patients, including their side effects. Nurses observe patients to determine the effects and side effects of the administered drugs, and then report these to doctors. Each specialist plays a role, allowing medication to be completed. However, in order to fully attain the effects of a drug, we need to consider the method of its administration. For example, it is difficult to attain the effects of laxatives for a person who eats irregularly; however, they are uniformly administered. Pharmacology education in nursing focuses on the mechanism of drugs and the way of maintaining their therapeutic effects and safeness, based on the viewpoint of "curing". Furthermore, nursing science focuses on the differences in efficacy depending on the characteristics of a patient, and also on the side effects of drugs, based on the viewpoint of "caring". However, education where care and cure are integrated needs to be provided, so that nurses can acquire applied skills to consider individual patient's bodies, lives, and psychological situations comprehensively, and then suggest the optimal method of administration. Also, there is Eastern medicine as well as Western medicine. Administration of Chinese medicine should be related to the patient's lifestyle. Nurses have to learn how each medicine is related to the patient's lifestyle, and what aspects in the patient they have to focus on.

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.

Aging-like physiological changes in the skin of Japanese obese diabetic patients.

OBJECTIVE: Obesity-associated diabetes causes aging-like changes to skin physiology in animal models, but there have been no clinical studies focusing on human obese diabetic patients. The purpose of this study was to examine the hypothesis that obesity-associated diabetes accelerates aging-like skin changes in Japanese people. METHODS: This cross-sectional study enrolled obese-diabetes patients (body mass index ≥ 25 kg m-2) and healthy volunteers (body mass index < 25 kg m-2) as controls. Skin physiology parameters relating to aging (stratum corneum hydration, transepidermal water loss, skin pH, advanced glycation end-products, and dermal collagen density) were evaluated in the two groups. RESULTS: About 37 subjects participated (16 in a control group and 21 in an obese-diabetes group). Age was not significantly different between the groups. The stratum corneum hydration level was significantly lower in the obese-diabetes group. Transepidermal water loss and levels of advanced glycation end-products were significantly higher in this group. Skin pH was not significantly different between groups. Dermal collagen density decreased in the obese-diabetes group. CONCLUSION: We showed that obese-diabetes patients have decreased stratum corneum hydration, increased transepidermal water loss, higher skin advanced glycation end-products and decreased dermal collagen fiber density compared with normal-weight subjects. These results indicate that the ordinary age-related physiological skin changes seen in the elderly can also occur in obese-diabetes patients aged in their 40s.

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.

Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.

Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5'-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.

CRMP1 and CRMP2 have synergistic but distinct roles in dendritic development.

Collapsin response mediator protein 2, CRMP2, has been identified as an intracellular signaling mediator for Semaphorin 3A (Sema3A). CRMP2 plays a key role in axon guidance, dendritic morphogenesis, and cell polarization. It has been also implicated in a variety of neurological and psychiatric disorders. However, the in vivo functions of CRMP2 remain unknown. We generated CRMP2 gene-deficient (crmp2(-/-) ) mice. The crmp2(-/-) mice showed irregular development of dendritic spines in cortical neurons. The density of dendritic spines was reduced in the cortical layer V pyramidal neurons of crmp2(-/-) mice as well as in those of sema3A(-/-) and crmp1(-/-) mice. However, no abnormality was found in dendritic patterning in crmp2(-/-) compared to wild-type (WT) neurons. The level of CRMP1 was increased in crmp2(-/-) , but the level of CRMP2 was not altered in crmp1(-/-) compared to WT cortical brain lysates. Dendritic spine density and branching were reduced in double-heterozygous sema3A(+/-) ;crmp2(+/-) and sema3A(+/-) ;crmp1(+/-) mice. The phenotypic defects had no genetic interaction between crmp1 and crmp2. These findings suggest that both CRMP1 and CRMP2 mediate Sema3A signaling to regulate dendritic spine maturation and patterning, but through overlapping and distinct signaling pathways.

Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.

Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

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.

Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling.

Aging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging-like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging-like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV-evoked aging-like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging-like skin in the UV-irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging-like changes in the skin. The 2-week UV onto the non-MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.

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.

Novel models for bacterial colonization and infection of full-thickness wounds in rats.

An animal model is needed to study the pathophysiology of wound infections; however, an animal model that is reproducible and clinically relevant has not previously been available. In addition, an animal model of wound colonization generated in a manner similar to the wound infection model would be useful. Here, we describe new animal models of the wound infection continuum for the characterization of essential host-pathogen relationships. We determined the conditions needed to establish rat models of stable wound colonization and infection, without the use of disturbing factors (e.g., foreign bodies or induction of diabetes mellitus). We found that the age of the rats, bacterial inoculum size, and wound location were important elements in generating reproducible, obvious, spreading wound infections. We inoculated approximately 6-month-old rats with 2.06 × 10(9) or 4.12 × 10(9) colony-forming units of Pseudomonas aeruginosa to generate the wound colonization and wound infection models, respectively. Wounds were made 2 cm cranial to the greater trochanter. These clinically relevant and highly reproducible animal models can be used to investigate the mechanisms of wound infection and monitor the effect of therapeutic agents in vivo.

Altered expression of matrix metalloproteinases and their tissue inhibitors in matured rat adipocytes in vitro.

Obesity is recognized as a risk factor for delayed cutaneous wound healing. The authors hypothesized that the secretion of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) from subcutaneous adipose tissue correlates with disorder of the healing process in obese subjects. Findings from previous studies on the expression of MMPs and TIMPs in obese adipose tissue are inconsistent. Since these conflicting results could be due to the effect of several intrinsic factors, the authors conducted a simple in vitro experiment to clarify the change in profile of MMPs and TIMPs in excessively matured adipocytes. The authors cultured the induced adipocytes under conditions of high or low glucose and with or without insulin supplementation. Oil red O staining and its dye extraction assay revealed excessive lipid accumulation in high glucose and insulin-supplemented adipocytes. Additionally, there was altered expression of adipokines, similar to the change in adipose tissue in obese subjects. Under these conditions, the expression/activity of MMP8 was promoted and the expression of MMP3 and TIMP3 was inhibited. Further studies to determine the effect of other obesity-related factors, such as insulin resistance, on MMPs and TIMPs are required.