Clinical outcomes of perforator-based propeller flaps versus free flaps in soft tissue reconstruction for lower leg and foot trauma: a retrospective single-centre comparative study.

BACKGROUND: The efficacy and safety of perforator-based propeller flaps (PPF) versus free flaps (FF) in traumatic lower leg and foot reconstructions are debated. PPFs are perceived as simpler due to advantages like avoiding microsurgery, but concerns about complications, such as flap congestion and necrosis, persist. This study aimed to compare outcomes of PPF and FF in trauma-related distal lower extremity soft tissue reconstruction. METHODS: We retrospectively studied 38 flaps in 33 patients who underwent lower leg and foot soft tissue reconstruction due to trauma at our hospital from 2015 until 2022. Flap-related outcomes and complications were compared between the PPF group (18 flaps in 15 patients) and the FF group (20 flaps in 18 patients). These included complete and partial flap necrosis, venous congestion, delayed osteomyelitis, and the coverage failure rate, defined as the need for secondary flaps due to flap necrosis. RESULTS: The coverage failure rate was 22% in the PPF group and 5% in the FF group, with complete necrosis observed in 11% of the PPF group and 5% of the FF group, and partial necrosis in 39% of the PPF group and 10% of the FF group, indicating no significant difference between the two groups. However, venous congestion was significantly higher in 72% of the PPF group compared to 10% of the FF group. Four PPFs and one FF required FF reconstruction due to implant/fracture exposure from necrosis. Additionally, four PPFs developed delayed osteomyelitis post-healing, requiring reconstruction using free vascularized bone graft in three out of four cases. CONCLUSIONS: Flap necrosis in traumatic lower-leg defects can lead to reconstructive failure, exposing implants or fractures and potentially causing catastrophic outcomes like osteomyelitis, jeopardizing limb salvage. Surgeons should be cautious about deeming PPFs as straightforward and microsurgery-free procedures, given the increased complication rates compared to FFs in traumatic reconstruction. DATA ACCESS STATEMENT: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

A simple free flap strategy using end-to-side anastomosis to the main vessels in injured extremity.

Background: During free flap surgery, the surgeon sometimes encounters problems with anastomosis such as intractable arterial spasms or vessel size discrepancy in venous anastomoses. End-to-side (ETS) anastomosis has the advantages of limited chance of vessel spasm and easy handling by adjusting for vessel size discrepancy. We introduced the arterial and venous end-to-side anastomosis (AV-ETS) strategy, which is based on the ETS anastomosis to the main artery and accompanying veins, to avoid intraoperative anastomotic problems when creating a free flap. The aim of this study was to compare flap outcomes and intraoperative anastomotic problems before and after introduction of the AV-ETS strategy in extremity free flap surgery. Materials and methods: We retrospectively examined 72 consecutive extremity free flaps. Before introducing the AV-ETS strategy, we used the conventional strategy in which the recipient artery was selected according to the number of the remaining main artery and the anastomosis technique was flexibly changed, although the end-to-end (ETE) technique was used in most cases. Results: The conventional group had 18 flaps and the AV-ETS group had 54 flaps. The rate of flap survival did not differ between these groups, and there were no cases of flap failure after the introduction of the AV-ETS strategy. The AV-ETS group had significantly fewer flaps that required a change in preoperative planning for the recipient artery or anastomotic site of the artery. Conclusions: The AV-ETS strategy may facilitate reliable preoperative planning and the performance of stable free flap surgery without requiring a flexible response during surgery.

Asymmetric dimethylarginine accumulation under hyperglycemia facilitates ß-cell apoptosis via inhibiting nitric oxide production.

Low concentrations of nitric oxide (NO) produced by constitutive NO synthase (cNOS) has been shown to suppress apoptosis in pancreatic ß-cells. In the present study, the influence of asymmetric dimethylarginine (ADMA), the major endogenous inhibitor of NOS, on the apoptosis-suppressive effect of NO was investigated. The expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), an ADMA-metabolizing enzyme, in INS-1 ß-cells and in mouse pancreatic islets was drastically reduced by in vitro exposure to high-concentration glucose (20 mM) and by in vivo treatment of mice with the insulin receptor blocker S661, which resulted in hyperglycemia, respectively. In line with this, a higher ADMA level was observed in INS-1 cells exposed to 20 mM glucose. The treatment of INS-1 cells with ADMA, similarly to with the NOS inhibitor NG-nitro-L-arginine methyl ester, significantly facilitated 20 mM glucose-induced increase in cleaved caspase-3 protein expression. Furthermore, increased protein expression of cleaved caspase-3 and CHOP was observed in INS-1 cells with knockdown of DDAH2. These results suggest that ADMA accumulation through a decrease in DDAH2 expression in ß-cells, which is induced under hyperglycemic conditions, facilitates ß-cell apoptosis through suppression of cNOS-mediated NO production.

Efficacy of the microscopic parachute end-to-side technique for creating large-to-small venous anastomoses in free flaps in the extremities.

Purpose: The availability of reliable and suitably sized veins is limited for creating free flaps to treat severe trauma and infection, and it is important to manage vessel size discrepancy between the recipient and flap veins. We evaluated the clinical outcomes of free flaps with large-to-small venous end-to-side (ETS) anastomoses using the microscopic parachute end-to-side (MPETS) anastomosis in soft tissue defects in the extremities. This procedure comprises mainly a wide-slit venotomy and parachute procedure at the heel. Methods: We examined 24 free flaps in 23 patients given a large-to-small venous anastomosis using the MPETS technique. Patient demographics, details of vessel anastomoses, and flap outcomes and complications were obtained from medical records. Results: Two veins were anastomosed in six flaps. Thirty anastomosed veins were assessed, and 24 deep veins, all of which accompanied main arteries, were chosen as recipient veins. The mean diameters were 1.5 mm in the recipient veins and 2.7 mm in the flap veins, and the mean vessel size discrepancy was 1.8-fold (range 1.3-3.3 fold). Because of the presence of venous valves at the anastomotic site, trimming of venous cusps was performed in six veins. All flaps survived, though one venous thrombosis occurred because of pedicle kinking in a case with a short pedicle. Conclusions: The MPETS technique is simple, reliable, and useful for performing various types of venous anastomoses regardless of a vessel size discrepancy and the presence of a venous valve. This may be a good option for large-to-small venous anastomosis in free flaps.

Simultaneous Bilateral Proximal Humerus Fractures Treated with Single-Stage Bilateral Reverse Shoulder Arthroplasty.

Introduction: Simultaneous bilateral fractures of the proximal humerus are infrequent, and simultaneous bilateral three- or four-part fractures are even rarer. Reverse shoulder arthroplasty (RSA) is being used increasingly for the treatment of three- and four-part fractures of the proximal humerus. However, treatment of simultaneous bilateral fractures of the proximal humerus is difficult because of concern about postoperative immobilization and rehabilitation. Case Presentation. A 75-year-old woman presented with bilateral shoulder pain subsequent to a fall on the street. Physical examination and radiographs showed simultaneous bilateral fractures of the proximal humerus. The right side fracture was classified as a four-part fracture and the left side fracture as a three-part fracture, according to Neer's classification. The right shoulder had a risk of avascular necrosis of the humeral head. For the left shoulder, the fracture type had caused ischemia of the humeral head. Single-stage bilateral RSA was performed 9 days after the injury. An abduction pillow was applied for 5 weeks postoperatively. Passive motion exercises were permitted starting at 4 weeks postoperatively, and active range of motion exercises were permitted at 6 weeks postoperatively. At the patient's most recent follow-up 30 months after surgery, the patient reported no restriction of the activities of daily living. Radiographs revealed no lucent line on the humerus and glenoid components, although bone resorption and superior retraction of the tuberosities on both sides were observed. Conclusions: Single-stage bilateral RSA improved shoulder function, but healing of the greater tuberosity can affect the improvement in external rotation after the operation. Although a long-term follow-up is needed, single-stage bilateral RSA appears to be a viable treatment option.

Functional reconstructions using only ulnar nerve and ulnar nerve-innervated muscles for traumatic musculocutaneous, median and radial nerve palsies.

A 20-year-old right-handed fisherman experienced a severe injury in a high-energy traffic accident. These injuries included a shaft fracture of the right humerus, open comminuted fracture of the right forearm and multiple peripheral nerve palsies involving the musculocutaneous, median and radial nerves. Six months after the initial treatment, the patient was referred to our hand surgeons for further treatment. Several operations for functional reconstruction using only the ulnar nerve and ulnar nerve-innervated muscles were performed: the main procedures included a partial ulnar nerve transfer for elbow flexion, flexor carpi ulnaris transfer for reconstruction of wrist and finger extension and opponensplasty using the abductor digiti minimi. Three years after the initial injury, the patient had relatively good function including elbow flexion and stable side pinch and grasp. Functional reconstruction using a combination of the ulnar nerve and ulnar nerve-innervated muscles may be useful in specific cases involving multiple peripheral nerve injuries.

Blood flow distribution after end-to-side anastomosis with wide arteriotomy in extremity free flap surgery.

PURPOSE: Although many studies have investigated the optimal anastomotic procedure for the end-to-side (ETS) procedure with a free flap, no study has focused on the size of the arteriotomy. Some surgeons have recently described the effectiveness of ETS with wide arteriotomy, but the postoperative haemodynamics remains unclear for free flaps created using this technique. The aim of this study was to use ultrasonography to evaluate the postoperative blood flow distribution after ETS with a wide arteriotomy in extremity free flap surgery. METHODS: We evaluated 20 free flaps in 18 consecutive patients who received an ultrasonographic examination after free flap surgery using the ETS technique with wide arteriotomy for arterial anastomosis. All flaps were examined after surgery and blood flow was calculated for the flap and recipient vessels. RESULTS: All 20 flaps survived, but one flap developed asymptomatic arterial thrombosis and 19 flaps were analysed. For the ETS technique with wide arteriotomy, peripheral circulation was well preserved in all flaps. Comparison of flap types showed that blood flow was significantly higher in myocutaneous flaps than in fasciocutaneous flaps, but there was no significant difference according to the size of the arteriotomy. CONCLUSIONS: Given the range of arteriotomy performed using the ETS with a wide arteriotomy technique, the blood flow volume in the flap depended on the type of flap but not on the size of the arteriotomy. A steal phenomenon related to the creation of a wide window in the receipt artery was not found in the analysed retrospective cohort.

Diacylglycerol kinase δ functions as a proliferation suppressor in pancreatic ß-cells.

Although an aberrant reduction in pancreatic ß-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of ß-cell mass is poorly understood. Here, we show that diacylglycerol kinase δ (DGKδ) is a key enzyme in the regulation of ß-cell mass. DGKδ expression was detected in the nucleus of ß-cells. We developed ß-cell-specific DGKδ knockout (ßDGKδ KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of ßDGKδ KO mice. DGKδ knockdown in the ß-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and ß-cell loss were alleviated in ßDGKδ KO mice. Thus, suppressing the expression or enzymatic activity of DGKδ that functions as a suppressor of ß-cell proliferation could be a novel therapeutic approach to increase ß-cell mass for the treatment of diabetes.

Reliable free flaps using the microscopic parachute end-to-side technique in severe extremity injuries.

PURPOSE: Although end-to-side anastomosis is an essential method for the transfer of free flaps in traumatic extremity injuries, orthoplastic surgeons have no standard technique for performing this procedure. We describe a simple and reliable end-to-side technique is modified from that commonly used by cardiovascular surgeons for free-flap transfer. METHODS: Our microscopic parachute end-to-side technique consists primarily of two simple steps. First, the donor vessel is cut and widened with microscissors, and a wide slit is made in the recipient vessel. Second, the heel of the vessel is sutured using the parachute technique, followed by suturing of the vessel wall with a continuous suture to control blood leakage from the widely opened window. We retrospectively evaluated the clinical outcomes of 18 flaps in which the microscopic parachute end-to-side technique was used for both arterial and venous anastomoses. RESULTS: All microscopic parachute end-to-side procedures achieved flap survival without complications related to anastomosis. The mean size of the vesselotomy was 4.8 mm, and the mean expansion rate of the donor vessel was 2.7 times. CONCLUSIONS: Compared with the conventional end-to-side technique, the microscopic parachute end-to-side technique has three advantages: easy vesselotomy, avoidance of anastomotic narrowing, and easy control of blood leakage from the anastomotic site. We believe that the microscopic parachute end-to-side technique might make free flaps easier and improve their clinical outcomes in severe extremity injuries.

Adipose tissue complement factor B promotes adipocyte maturation.

OBJECTIVES: It is well-known that the complement system plays an essential role in host immunity. Observational studies have indicated that complement system-related molecules such as complement factor B (CfB) and other components are correlated with obesity and/or insulin resistance parameters. In this study, we investigated the role of adipocyte-derived CfB in adipose tissue metabolism. METHODS: We investigated the expression level of complement system-related genes in adipocytes. To understand the role of CfB in adipocyte, we performed Cfb overexpression in 3T3-L1 preadipocytes and generated adipocyte-specific Cfb transgenic mice. RESULTS: Cfb expression was markedly enhanced in 3T3-L1 adipocytes co-cultured with macrophages following endotoxin stimulation. In Cfb-overexpressing cells, the expression of adipocyte differentiation/maturation-related genes encoding peroxisome proliferator-activated receptor γ (Pparγ), adipocyte Protein 2 and perilipin was significantly enhanced. Cfb transgenic mice showed a marked increase in the expression of genes encoding Pparγ, perilipin, sterol regulatory element-binding protein 1 c, and Cd36 in the subcutaneous adipose tissue. CONCLUSIONS: CfB plays a crucial role in late-phase of adipocyte differentiation and subsequent lipid droplet formation.

"Half-folded" pedicled scapular bone flap for nonunion after humeral neck fracture: A case report.

Treatment of a nonunion of the proximal humerus remains a challenge because of the small proximal fragment and poor central cancellous bone stock of the humeral head. In this report, we describe our experience using a "half-folded" pedicled scapular bone flap with an anatomical locking plate to treat an atrophic nonunion of the proximal humerus in a 64-year-old right-handed woman. The patient had fallen and experienced a common humeral neck fracture 2.5 years previously. During the operation, we elevated the pedicled scapular bone flap, which measured 8.0 cm long and 1.5 cm wide, with a vascular pedicle about 10 cm long. We modified the bone flap to the half-folded type to fill the massive bone cavity in the humeral head. The proximal tip of the flap was divided into two segments while keeping the ventral soft tissue intact. The grafted bone bridging between the head and shaft of the humerus was rigidly fixed with a plate and screw. The operated shoulder was fixed with a sling and a chest belt for 3 weeks, after which the patient began active motion exercises of the shoulder joint. The flap survived without serious donor site morbidity, and good bone healing was obtained about 3.5 months after surgery. The patient was able to use the shoulder comfortably in daily activity without any serious donor site morbidity at 16 months after the surgery. This procedure may be effective in treating nonunion of the proximal humerus with a massive bone cavity in the humeral head.

Dependence of purple membrane bump curvature on pH and ionic strength analyzed using atomic force microscopy combined with solvent exchange.

Purple membrane (PM), which is a membrane patch formed by the self-assembly of the membrane protein bacteriorhodopsin (bR) with archaeal lipids, is a good subject for studying the mechanism for the supramolecular structural formation of membrane proteins. Several studies have suggested that PM is not simply planar but that it has a curvature. Atomic force microscopy (AFM) studies also indicate the presence of dome-like structures (bumps) on the cytoplasmic surface of PM. PM must have a curvature to form the bump structures; therefore, bump formations will be related to a mechanism for supramolecular structural formation via self-assembly. To elucidate the effect of an asymmetric distribution of charged residues between two aqueous domains on the bump curvature, AFM topography of identical PM sheets were examined with variation of the solvent ionic strength and pH using a newly constructed solvent circulation system. The radius and height distributions of the bumps on the identical PM sheets indicated a linear correlation. The bump curvature, which was simply estimated by the slope of the distribution, became smaller with increasing KCl concentration, which suggests that tension at the cytoplasmic surface caused by electrostatic repulsive force between negatively charged amino acid residues becomes weaker by the electrostatic shielding effect. AFM observations revealed that the bump curvature remained even at high KCl concentration where the Debye length is within a few Angstroms; therefore, the contribution of the intrinsic difference between the domain sizes of bR between two sides was confirmed. Interestingly, the bump curvature was significantly increased by the addition of CaCl2 and then decreased with a similar dependency to KCl at higher CaCl2 concentration. The effect of pH on the bump curvature was also examined, where the curvature increased and reached a maximum at pH 9, while it decreased above pH 10, at which point the two-dimensional crystalline lattice of bR began to disassemble. These experimental results indicate that the bump curvature is strongly influenced by electrostatic interactions. A plausible model for bump structure formation by electrostatic repulsive force is presented based on these results.

Circulating TNF receptor 2 is closely associated with the kidney function in non-diabetic Japanese subjects.

AIM: Chronic kidney disease (CKD) is associated with cardiovascular events. Tumor necrosis factor (TNF) and/or its receptors have been postulated to be involved in renal pathophysiology. It is unclear whether an increased TNF system activity is present before the development of apparent CKD. METHODS: Four hundred and twenty non-diabetic Japanese subjects with an estimated GFR (eGFR) greater than 60 ml/min/1.73 m(2) were recruited for measurement of the HbA1c, insulin, TNF system activity (TNF-α, soluble TNF receptor 1 (sTNF-R1) and sTNF-R2) levels and various parameters, including the lipid, high-sensitivity C-reactive protein (hsCRP), high-molecular-weight (HMW) adiponectin and leptin levels. The subjects were stratified according to the eGFR: the G1 level (eGFR ≧90 ml/min/1.73 m(2)) and the G2 level (90 ＞eGFR ≧60 ml/min/1.73 m(2)). RESULTS: Whereas no significant differences were observed in gender, body mass index (BMI), blood pressure, insulin, TNF-α, hsCRP, HMW adiponectin or leptin between the two groups, the values for age, HbA1c, triglycerides, sTNF-R1 and sTNF-R2 were significantly higher in the subjects with a G2 level of eGFR than in those with a G1 level. In contrast, the HDL cholesterol levels were significantly lower in the subjects with a G2 level than in those with a G1 level. Linear negative correlations were also observed between eGFR and age, BMI, HbA1c, triglycerides, sTNF-R1 and sTNFR2, respectively. A multiple logistic regression analysis revealed that only sTNF-R2 was associated with the presence of a G2 level of eGFR (Odds ratio 1.092, 95% CI 1.013-1.177, P=0.021). CONCLUSIONS: The circulating sTNF-R2 level is closely associated with the kidney function in non-diabetic Japanese subjects.

The inflammation-lipocalin 2 axis may contribute to the development of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD. METHODS: The study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach. RESULTS: DNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid. CONCLUSIONS: Since an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.

Lifestyle factors associated with gastroesophageal reflux disease in the Japanese population.

BACKGROUND: We aimed to clarify the lifestyle factors associated with erosive esophagitis and non-erosive reflux disease (NERD) in a Japanese population. METHODS: Among 886 subjects who underwent health screening, we selected, according to their scores on the FSSG (frequency scale for symptoms of gastroesophageal reflux disease; GERD) questionnaire and the findings of upper gastrointestinal endoscopy, 138 subjects with erosive esophagitis (EE), 148 subjects with NERD (absence of esophagitis, FSSG score ≥8, and acid reflux-related symptoms score ≥4), and 565 control subjects (absence of esophagitis and FSSG score ≤7). We compared clinical characteristics and various lifestyle factors in these three groups. RESULTS: The lifestyle factors significantly associated with NERD compared with findings in the control group were intake of egg (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.01-3.50), sleep shortage (OR 2.44, 95% CI 1.54-3.88), and strong psychological stress (OR 1.77, 95% CI 1.18-2.62). In male subjects, current smoking (OR 2.06, 95% CI 1.13-3.74; OR 1.87, 95% CI 1.09-3.20) was a significant risk factor for both NERD and EE. Moreover, alcohol >200 kcal/day (OR 3.99, 95% CI 1.03-15.55) and intake of a large quantity of food at supper (OR 7.85, 95% CI 1.66-37.05) were significant risk factors for EE in subjects with hiatal hernia. Intake of a large quantity of food at supper (OR 2.09, 95% CI 1.06-4.13) was more common in the NERD group than in the EE group. CONCLUSIONS: There were differences in the associated lifestyle factors between patients with NERD and those with EE, and there was also a gender-related difference between these groups.

Reduction of visceral fat correlates with the decrease in the number of obesity-related cardiovascular risk factors in Japanese with Abdominal Obesity (VACATION-J Study).

AIM: Visceral fat accumulation is associated with obesity-related cardiovascular risk factor accumulation and atherosclerosis. The present study investigated whether one-year reduction of the visceral fat area (VFA) correlates with a decrease in the number of such factors in Japanese with or without visceral fat accumulation. METHODS: The study subjects comprised 5,347 Japanese, who underwent health check-ups in 2007 and 2008, including measurements of VFA and subcutaneous fat area (SFA) by computed tomography at 9 centers in Japan. Subjects with one or more such factor(s) were categorized into tertiles based on the one-year change in VFA. We investigated the multivariate age, sex, and one-year change in SFA-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for reductions in the number of risk factors in each of the three categories based on the one-year change in VFA, in subjects with one or more such factors (n= 3,648). RESULTS: In the entire group (n=3,648), the OR and 95%CI for reductions in the number of risk factors in the first tertile were 0.804 (0.673-0.962, p=0.0172), compared with the second tertile set at 1.0. Subjects with VFA <100cm(2) showed no reduction in the number of risk factors. In subjects with VFA≥100 cm(2), OR in the first tertile was 0.788 (0.639-0.972, p=0.0257) relative to the second tertile set at 1.0. CONCLUSIONS: In subjects with multiple cardiovascular risk factors, visceral fat reduction correlated with a decrease in the number of such factors in subjects with VFA≥100cm(2), but not in those with VFA<100cm(2).

Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers.

BACKGROUND: The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels. METHODS: We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS). RESULTS: In subjects with BMI below 25 kg/m2, both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m2, smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS. CONCLUSIONS: Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than non-smokers.

Absolute value of visceral fat area measured on computed tomography scans and obesity-related cardiovascular risk factors in large-scale Japanese general population (the VACATION-J study).

BACKGROUND: The management of cardiovascular risk factors is important for prevention of atherosclerotic cardiovascular diseases (ACVD). Visceral fat accumulation plays an important role in the clustering of cardiovascular risk factors, leading to ACVD. The present study investigated the gender- and age-specific relationship between obesity-related cardiovascular risk factor accumulation and computed tomography (CT)-measured fat distribution in a large-scale Japanese general population. METHODS AND RESULTS: Fat distribution was measured on CT scans in 12,443 subjects (males/females = 10,080/2,363), who underwent medical health check-up at 9 centers in Japan. The investigated obesity-related cardiovascular risk factors were hyperglycemia, dyslipidemia, and elevated blood pressure. Visceral fat area (VFA) for all males and old females showed almost symmetric distribution, while that of young females showed skewed distribution with a marked left shift. Only a small proportion of young females had large visceral fat and cardiovascular risk accumulation. The mean number of risk factors exceeded 1.0 at around 100 cm(2) for VFA in all groups, irrespective of gender, age (cut-off age 55), and BMI (cut-off BMI 25 kg/m(2)). CONCLUSIONS: In this large-scale Japan-wide general population study, an absolute VFA value of about 100 cm(2) equated with obesity-related cardiovascular risk factor accumulation, irrespective of gender, age, and BMI.

Smoking, white blood cell counts, and TNF system activity in Japanese male subjects with normal glucose tolerance.

BACKGROUND: Cigarette smokers have increased white blood cell (WBC) counts and the activation of tumor necrosis factor (TNF). The effect of smoking on WBC counts and TNF system activity, however, has not been separately investigated yet. SUBJECTS AND METHODS: One hundred and forty-two Japanese male subjects with normal glucose tolerance were recruited. They were stratified into two groups based on the questionnaire for smoking: one with current smokers (n = 48) and the other with current non-smokers (n = 94). Whereas no significant differences were observed in age, BMI, high molecular weight (HMW) adiponectin, and TNF-α between the two groups, current smokers had significantly higher soluble TNF receptor 1 (sTNF-R1) (1203 ± 30 vs. 1116 ± 21 pg/ml, p = 0.010) and increased WBC counts (7165 ± 242 vs. 5590 ± 163/µl, p < 0.001) and lower HDL cholesterol (55 ± 2 vs. 60 ± 1 mg/dl, p = 0.031) as compared to current non-smokers. Next, we classified 48 current smokers into two subpopulations: one with heavy smoking (Brinkman index ≥ 600) and the other with light smoking (Brinkman index < 600). RESULTS: Whereas no significant difference was observed in age, BMI, HMW adiponectin, WBC counts and TNF-α, sTNF-R1 and sTNF-R2 were significantly higher in heavy smoking group (1307 ± 44 vs. 1099 ± 30 pg/ml, p < 0.001; 2166 ± 86 vs. 827 ± 62 pg/ml, p = 0.005) than in light smoking group, whose sTNF-R1 and sTNF-R2 were similar to non-smokers (sTNF-R1: 1116 ± 15 pg/ml, p = 0.718, sTNF-R2; 1901 ± 32 pg/ml, p = 0.437). In contrast, WBC counts were significantly increased in heavy (7500 ± 324/µl, p < 0.001) or light (6829 ± 352/µl, p = 0.001) smoking group as compared to non-smokers (5590 ± 178/µl). There was no significant difference in WBC counts between heavy and light smoking group (p = 0.158). CONCLUSION: We can hypothesize that light smoking is associated with an increase in WBC counts, while heavy smoking is responsible for TNF activation in Japanese male subjects with normal glucose tolerance.

Measuring the sizes of nanospheres on a rough surface by using atomic force microscopy and a curvature-reconstruction method.

One of the advantages of atomic force microscopy (AFM) is that it can accurately measure the heights of targets on flat substrates. It is difficult, however, to determine the shape of nanoparticles on rough surfaces. We therefore propose a curvature-reconstruction method that estimates the sizes of particles by fitting sphere curvatures acquired from raw AFM data. We evaluated this fitting estimation using 15-, 30-, and 50-nm gold nanoparticles on mica and confirmed that particle sizes could be estimated within 5% from 20% of their curvature measured using a carbon nanotube (CNT) tip. We also estimated the sizes of nanoparticles on the rough surface of dried cells and found we also can estimate the size of those particles within 5%, which is difficult when we only used the height information. The results indicate the size of nanoparticles even on rough surfaces can be measured by using our method and a CNT tip.