Function of the hand as a predictor of early diagnosis and progression of Alzheimer's dementia: A systematic review.

BACKGROUND: The dominant feature of Alzheimer's dementia (AD) is gradual cognitive decline, which can be reflected by reduced finger dexterity. OBJECTIVE: This review analyzed reports on hand function in AD patients to determine the possibility of using it for an early diagnosis and for monitoring the disease progression of AD. METHODS: PubMed, Web of Science, EMBASE, and Cochrane library were searched systematically (search dates: 2000-2022), and relevant articles were cross-checked for related and relevant publications. RESULTS: Seventeen studies assessed the association of the handgrip strength or dexterity with cognitive performance. The hand dexterity was strongly correlated with the cognitive function in all studies. In the hand dexterity test using the pegboard, there was little difference in the degree of decline in hand function between the healthy elderly (HE) group and the mild cognitive impairment (MCI) group. On the other hand, there was a difference in the hand function between the HE group and the AD group. In addition, the decline in hand dexterity is likely to develop from moderate to severe dementia. In complex hand movements, movement speed variations were greater in the AD than in the HE group, and the automaticity, regularity, and rhythm were reduced. CONCLUSIONS: HE and AD can be identified by a simple hand motion test using a pegboard. The data can be used to predict dementia progression from moderate dementia to severe dementia. An evaluation of complex hand movements can help predict the transition from MCI to AD and the progression from moderate to severe dementia.

The Aqueous Extract of Radio-Resistant Deinococcus actinosclerus BM2T Suppresses Lipopolysaccharide-Mediated Inflammation in RAW264.7 Cells.

Deinococcus actinosclerus BM2T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC50 = 349.3 µg/ml) and ORAC (IC50 = 50.24 µg/ml) assays. At 20 µg/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 µg/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.

Secondary Fermented Extract of Chaga-Cheonggukjang Attenuates the Effects of Obesity and Suppresses Inflammatory Response in the Liver and Spleen of High-Fat Diet-Induced Obese Mice.

Cheonggukjang and chaga mushrooms have numerous health benefits, and have been used in alternative medicine. Therefore, a powder mixture of 98: Cheonggukjang and 2: Chaga extracts was fermented with Lactobacillus acidophilus KCTC3925 (FCC) and its anti-obesity effects in high-fat diet (HFD)-induced obese mice were determined. Five-week-old male ICR mice were fed a normal diet or HFD in the presence or absence of 3% and 5% FCC by weight (n = 10 per group). After 12 weeks, the mice were sacrificed, and the serum and tissue samples were collected for analysis. Body weight and epididymal fat pad weight were significantly lowered in the 3% and 5% FCC groups compared with those in the HFD control group (p < 0.01). FCC supplementation suppressed serum triglyceride and increased serum HDL-C levels (p < 0.01). Serum GOT, GPT, and leptin levels, hepatic COX-2 mRNA expression, and splenic COX-2 and IL-4 mRNA expression were significantly higher in the HFD groups than in the control group (p > 0.05); however, except for splenic IL-4 levels, the increases were significantly attenuated by FCC supplementation. Expression of ICAM-1, an aortic inflammatory marker, was significantly increased in the HFD group; this effect was suppressed in the 3% FCC group (p < 0.01) but not in the 5% FCC group. FCC suppressed the body weight and epididymal fat pad weight gain, as well as inflammatory responses in the liver and spleen of HFD-fed mice. Thus, FCC supplementation will be beneficial for the treatment of obesity-related effects.

Decursin and Z-Ligustilide in Angelica tenuissima Root Extract Fermented by Aspergillus oryzae Display Anti-Pigment Activity in Melanoma Cells.

The anti-melanogenic effects of the extract of Angelica tenuissima (AT) root and the extract of AT root fermented by Aspergillus oryzae (FAT) were investigated. These effects were determined by measuring the inhibitory activity of AT and FAT on melanin production in B16F10 melanocytes and with in vitro tyrosinase activity assays. The AT extract inhibited melanin production at concentrations above 250 µg/ml, and this inhibitory effect was significantly enhanced by the fermentation process with A. oryzae. HPLC analysis resulted in the isolation of two active compounds from both the AT and FAT extracts. Their chemical structures were identified as decursin and Z-ligustilide through comparison with previously reported NMR data. The decursin and Z-ligustilide contents were increased in the FAT extract and could be responsible for its enhanced inhibitory effects on melanin production and tyrosinase activity compared with that of the AT extract.

Changes in movements of neck, trunk, and hip according to height and foot position during sit-to-stand.

[Purpose] The purpose of this study is to analyze changes in movements of the neck, trunk and hip according to foot position while performing sit-to-stand (STS) exercises from a height-fixed chair. [Subjects and Methods] The study subjects consisted of 22 university students (12 males and 10 females). STS was conducted using a height-fixed chair at three positions: symmetric foot position, right foot position, and left foot position. Through three-dimensional motion analyzer, the movements of the neck, trunk, and hip were analyzed. [Results] While performing STS, the height was more influential on changed in angle of the neck, trunk, and hip. Moreover, when the height of the chair and the height of the subject were not matched correctly, more effective STS could be achieved when both of feet were laid symmetrically rather than at the other two positions. [Conclusion] It is necessary to employ an appropriate chair height that is matched with the height of the patients when therapy using STS is performed.

Effect of kinesio taping on the isokinetic muscle function in football athletes with a knee injury.

[Purpose] The purpose of this study was to determine the difference in isokinetic muscle function in football athletes with a knee injury with and without kinesio taping. [Subjects] The subjects for this study were 10 football athletes (males) with a knee injury. [Methods] Measurements were performed by using Cybex dynamometer under uniform motion before and after the application of kinesio tape to the quadriceps and hamstring muscle. Maximal concentric knee extension and flexion at three angular velocities (60°/s, 120°/s, and 180°/s) were measured. [Results] A significant difference was found in peak torque and total work of the flexion at 120°/s and 180°/s, as well as in the average power of extension at 180°/s. [Conclusion] Though it is not the main therapy for muscle function in football athletes with injury, kinesio taping was an effective adjunct therapy.

Effects of different sitting positions on skin temperature of the lower extremity.

[Purpose] The purpose of this study was to identify the effect of different sitting positions on the skin temperature of the lower extremity. [Subjects] The subjects of this study were 23 healthy university students (8 males, 15 females). [Methods] Normal sitting (NS), upper leg cross (ULC) and ankle on knee (AOK) positions were conducted to measure the changes in skin temperature using digital infrared thermographic imaging (DITI). [Results] ULC upper ankle, NS upper shin, ULC upper shin and NS lower shin showed significant declines in temperature with time. [Conclusion] These finding suggest that the ULC and NS sitting positions cause decline of blood flow volume to the lower extremity resulting in decrease of temperature of the lower extremity. Especially, sitting with the legs crossed interferes with the circulation of blood flowing volume much more than just sitting in a chair.

The effect of superficial trunk muscle exercise and deep trunk muscle exercise on the foot pressure of healthy adults.

[Purpose] The purpose of this study was to analyze the effect of superficial trunk muscle exercise and deep trunk muscle exercise on the foot pressure of healthy adults. [Subjects] The subjects were 30 healthy females and males who agreed to participate in this study. There were two groups, a superficial trunk muscle exercise group and a deep trunk muscle exercise group, with 15 participants in each. [Methods] The exercises were conducted 5 times a week for 4 weeks for both groups. A gait analyzer was used to measure foot plantar pressure while walking on a plate. Participants were measured before starting the exercise and after 4 weeks. The paired t-test was used to analyze the pre-and post-test results. [Results] There were no significant differences in foot pressure in any region in the superficial trunk muscle exercise group. In the deep trunk muscle exercise group, there were statistically significant increase in F1, F4, F5, R1 and R3. In addition, there were significant decreases in R2 and R4. [Conclusion] After the 4-week deep trunk muscle exercise group decreases in foot pressure on the inner foot and increases on the outside of the feet indicate normal and overall even distribution of body weight on the feet.

Fucoidan from Fucus vesiculosus protects against alcohol-induced liver damage by modulating inflammatory mediators in mice and HepG2 cells.

Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg) for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-ß1), a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-ß1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

Analysis of the risk factors of musculoskeletal disease among dentists induced by work posture.

[Purpose] The purpose of this study was to ergonomically evaluate the work posture of dentists to examine their subsequent risk of developing musculoskeletal diseases. [Subjects and Methods] Scenes in which the three dentists performed procedures at their dental clinics were videotaped. The videotapes of the dentists' work postures were evaluated and analyzed by using the Rapid Upper Limb Assessment (RULA) and Quick Exposure Check (QEC). [Results] The RULA analysis of the dentists' work posture indicated, "improvement required" in the posture used to treat the anterior and "instant improvement required" in the posture used to treat the maxillary second molar. Of all the work postures studied, the risk was considered particularly high in the lower back and neck, implying prominent problems in these body parts. The QEC analysis showed that the worst work posture was that required to treat the maxillary second molar, which led to a high risk of neck problems and vibrations. [Conclusion] The neck area has the highest risk of developing musculoskeletal disease. Hence, regular rests and the provision of information regarding muscle strengthening exercise for the neck are necessary.

The analgesic and anti-inflammatory effects of Litsea japonica fruit are mediated via suppression of NF-κB and JNK/p38 MAPK activation.

Fruits of the Litsea family of trees and shrubs contain biologically active compounds, some of which have been used as natural nutrients and flavoring agents in food. In this study, we identified novel anti-nociceptive effects of the 30% ethanol extract, the CH(2)Cl(2) fraction and the associated active components (Hamabiwalactone A and B) from Litsea japonica fruit by using in vivo peripheral and central nervous pain models. In addition, we compared the anti-inflammatory effects of several fractions from L. japonica fruit extracts using lipopolysaccharide (LPS)-stimulated Raw264.7 cells. The CH(2)Cl(2) fraction of L. japonica fruit (LJM) had an optimal combination of anti-inflammatory effects and low cytotoxicity. Dose response studies were performed to determine the inhibitory effects of LJM on the pro-inflammatory enzymes, COX-2/PGE(2) and NO/iNOS, and pro-inflammatory cytokines, IL-1ß, IL-6, and TNF-α. Molecular profiling revealed that LJM exerts anti-inflammatory effects through inhibition of NF-κB and JNK/p38 MAPK signaling in LPS-induced macrophages. This study suggests that CH2Cl2 fraction of L. japonica fruit and its bioactive components are potential candidates as anti-inflammatory and analgesic agents (painkillers) for the treatment of inflammatory diseases.

Effect of the combinatory mixture of Rubus coreanus Miquel and Astragalus membranaceus Bunge extracts on ovariectomy-induced osteoporosis in mice and anti-RANK signaling effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus and Astragalus membranaceus have been used for their various pharmacological properties in Asia as a traditional medicine. The present study evaluated the anti-osteoporotic effects of the optimal combination of Rubus coreanus and Astragalus membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX) mice by investigating bone biomechanical properties and the serum levels of TNF-α, osteocalcin, RANKL, OPG, and RANK-RANKL signal-related osteoclast differentiation markers. MATERIALS AND METHODS: A total of 36 mature female outbred ICR (Institute of cancer research) strain mice (7 weeks) were divided into 6 groups with 7 mice in each group as follows: (1) Sham-operated control mice (Sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through gavage. (2) OVX mice received a daily oral gavage of PBS (OVX). (3) OVX mice were treated daily with 50mg/kgb.w./day of RAM (4) with 100mg/kgb.w./day of RAM or (5) with 200mg/kgb.w./day of RAM via oral gavage. (6) OVX mice received i.p. injections of 17ß-estradiol (E2) (0.1mg/kgb.w./day) three times per week for 12 weeks. RESULTS: Micro-CT images showed that oral administration of RAM to OVX mice prevented tibial bone loss, preserved trabecular bone microarchitecture, and improved bone biomechanical properties. RAM administration also showed recovery effects on the levels of TNF-α, OPG and RANKL concentration in OVX-states. Additionally, we found that the mechanism by which RAM elicited anti-osteoporotic effects was by down-regulating the expression of TRAF6 and NFATc1 in RANKL-RANK pathway, a route of osteoclast differentiation, followed by reducing the production of osteoclast differentiation factors, calcitonin receptors and cathepsin K. CONCLUSIONS: Our research strongly suggests that RAM can be clinically used in the prevention and treatment of postmenopausal osteoporosis.

Effects of red ginseng on the regulation of cyclooxygenase-2 of spleen cells in whole-body gamma irradiated mice.

Exposure to gamma radiation causes a wide range of biological damage and alterations, including oxidative stress, inflammation and cancer. This study aimed to identify the radioprotective effect of Korean red ginseng extract (RG) against whole-body gamma-irradiation (γIR) in mice and the regulatory mechanisms of the radiosensitive gene in spleen, cyclooxygenase-2 (COX-2). RG was administered intraperitoneally (i.p.) or orally (p.o.) to C57BL/6 mice for five days, which were then exposed to 6.5 Gy of (137)Cs-γIR. Thymus and spleen were harvested after three days, and organ size and COX-2 expression of the spleen using Western blotting, were examined. γIR shrank both organs and RG recovered the size of thymus but not spleen. RG also significantly inhibited the increased expression of COX-2 induced by γIR. These results were similar following both routes of RG administration, however i.p. RG administration was more effective, thus it was used in progressive studies. In terms of COX-2 expression related intracellular factors, we found here that γIR activated the p38 MAPK, PI3K/Akt and HO-1 but not NF-κB or Nrf2. Activated p38 MAPK, PI3K/Akt and HO-1 were down-regulated by RG while the RG-induced COX-2 expression was only related to HO-1 activation. These results suggest that RG supplementation provides protective effects against radiation-induced inflammation and cancer, and its potential to be utilized in clinical trials and functional foods.

Effects of ß-glucans from Coriolus versicolor on macrophage phagocytosis are related to the Akt and CK2/Ikaros.

Coriolus versicolor has been known to be an immune stimulator effects. For further understanding of the phagocytic activity and the intracellular mechanisms of ß-glucan from C. versicolor (CVG), we examined the phagocytic activity, phosphorylation of Akt and CK2, nucleus translocation of p65 and Ikaros activity in ß-glucan-treated macrophages using RT-PCR, western blotting, and IP assay. The role of Ikaros in regulating phagocytic effects of CVG was also determined using Ikaros dominant negative isoform cells. This study suggests that CK2/Ikaros are positive regulators and novel signaling pathway involved in phagocytosis and contributes to elucidating the mechanism underlying phagocytic activity induced by ß-glucan.

High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury.

OBJECTIVES: The angiogenic drive in skeletal muscle ischemia remains poorly understood. Innate inflammatory pathways are activated during tissue injury and repair, suggesting that this highly conserved pathway may be involved in ischemia-induced angiogenesis. We hypothesize that one of the endogenous ligands for innate immune signaling, high mobility group box 1 (HMGB1), in combination with autophagic responses to hypoxia or nutrient deprivation, plays an important role in angiogenesis. METHODS: Human dermal microvascular endothelial cells (ECs) were cultured in normoxia or hypoxia (1% oxygen). Immunocytochemical analysis of HMGB1 subcellular localization, evaluation of tube formation, and Western blot analysis of myotubule light-chain 3I (LC3I) conversion to LC3II, as a marker of autophagy, were conducted. 3-Methyladenine (3MA), chloroquine, or rapamycin were administered to inhibit or promote autophagy, respectively. In vivo, a murine hind limb ischemia model was performed. Muscle samples were collected at 4 hours to evaluate for nuclear HMGB1 and at 14 days to examine endothelial density. Perfusion recovery in the hind limbs was calculated by laser Doppler perfusion imaging (LDPI). RESULTS: Hypoxic ECs exhibited reduced nuclear HMGB1 staining compared with normoxic cells (mean fluorescence intensity, 186.9 ± 17.1 vs 236.0 ± 1.6, P = .01) with a concomitant increase in cytosolic staining. HMGB1 treatment of ECs enhanced tube formation, an angiogenic phenotype of ECs. Neutralization of endogenous HMGB1 markedly impaired tube formation and inhibited LC3II formation. Inhibition of autophagy with 3MA or chloroquine abrogated tube formation, whereas its induction with rapamycin enhanced tubing and promoted HMGB1 translocation. In vivo, ischemic skeletal muscle showed reduced numbers of HMGB1-positive myocyte nuclei compared with nonischemic muscle (34.9% ± 1.9% vs 51.7% ± 2.0%, P < .001). Injection of HMGB1 into ischemic hind limbs increased perfusion recovery by 21% and increased EC density (49.2 ± 4.1 vs 34.2 ± 3.4 ECs/high-powered field, respectively; P = .02) at 14 days compared with control hind limbs. CONCLUSIONS: Nuclear release of HMGB1 and autophagy occur in ECs in response to hypoxia or serum depletion. HMGB1 and autophagy are necessary and likely play an interdependent role in promoting the angiogenic behavior of ECs. In vivo, HMGB1 promotes perfusion recovery and increased EC density after ischemic injury. These findings suggest a possible mechanistic link between autophagy and HMGB1 in EC angiogenic behavior and support the importance of innate immune pathways in angiogenesis.

Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells.

Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing a nonfunctional, mutant form of TLR9, we identified a role of TLR9 in driving the initial cytokine response and liver damage in a model of hemorrhagic shock and bilateral femur fracture. Circulating DNA levels were found to correlate with the degree of tissue damage. Experiments using chimeric mice show that TLR9 on both bone marrow-derived cells and parenchymal cells are important for the TLR9-mediated liver and tissue damage, as well as systemic inflammation after HS/T. These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9.

Forskolin increases angiogenesis through the coordinated cross-talk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling.

Forskolin, a potent activator of adenylyl cyclases, has been implicated in modulating angiogenesis, but the underlying mechanism has not been clearly elucidated. We investigated the signal mechanism by which forskolin regulates angiogenesis. Forskolin stimulated angiogenesis of human endothelial cells and in vivo neovascularization, which was accompanied by phosphorylation of CREB, ERK, Akt, and endothelial nitric oxide synthase (eNOS) as well as NO production and VEGF expression. Forskolin-induced CREB phosphorylation, VEGF promoter activity, and VEGF expression were blocked by the PKA inhibitor PKI.Moreover, phosphorylation of ERK by forskolin was inhibited by the MEK inhibitor PD98059, but not PKI. The forskolin-induced Akt/eNOS/NO pathway was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, but not significantly suppressed by PKI. These inhibitors and a NOS inhibitor partially inhibited forskolin-induced angiogenesis. The exchange protein directly activated by cAMP (Epac) activator, 8CPT-2Me-cAMP, promoted the Akt/eNOS/NO pathway and ERK phosphorylation,but did not induce CREB phosphorylation and VEGF expression. The angiogenic effect of the Epac activator was diminished by the inhibition of PI3K and MEK, but not by the PKA inhibitor. Small interfering RNA-mediated knockdown of Epac1 suppressed forskolin-induced angiogenesis and phosphorylation of ERK, Akt, and eNOS, but not CREB phosphorylation and VEGF expression. These results suggest that forskolin stimulates angiogenesis through coordinated cross-talk between two distinct pathways, PKA-dependent VEGF expression and Epac-dependent ERKactivation and PI3K/Akt/eNOS/NO signaling.

Differential regulation of apoptosis by caspase-mediated cleavage of phospholipase D isozymes.

Phospholipase D (PLD) has been implicated in survival and anti-apoptosis, but the molecular mechanism by which it responds to apoptotic stimuli is poorly unknown. Here, we demonstrate that cleavage of PLD isozymes as specific substrates of caspase differentially regulates apoptosis. PLD1 is cleaved at one internal site (DDVD(545)S) and PLD2 is cleaved at two or three sites (PTGD(13)ELD(16)S and DEVD(28)T) in the front of N-terminus. Cleavage of PLD was endogenously detected in post-mortem Alzheimer brain together with activated caspase-3, suggesting the physiological relevance. The cleavage of PLD1 but not PLD2 might act as an inactivating process since PLD1 but not PLD2 activity is significantly decreased during apoptosis, suggesting that differential cleavage of PLD isozymes could affect its enzymatic activity. Moreover, caspase-resistant mutant of PLD1 showed more potent anti-apoptotic capacity than that of wild type PLD1, whereas PLD2 maintained anti-apoptotic potency in spite of its cleavage during apoptosis. Moreover, PLD2 showed more potent anti-apoptotic effect than that of PLD1 in overexpression and knockdown experiments, suggesting that difference in anti-apoptotic potency between PLD1 and PLD2 might be due to its intrinsic protein property. Taken together, our results demonstrate that differential cleavage pattern of PLD isozymes by caspase might affect its enzymatic activity and anti-apoptotic function.

Microscopic technique for the detection of nitric oxide-dependent angiogenesis in an animal model.

Nitric oxide (NO) plays an important role in maintaining vascular homeostasis. The importance of NO in the vasculature is demonstrated by several experimental conditions, such as vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the NO metabolic pathway in endothelial cells could be one of the main contributing factors for angiogenesis. Although several methods have been used for measuring in vitro angiogenesis, a proper technique has not been developed for identifying in vivo NO-dependent angiogenesis. This chapter provides a new intravital microscopic method for detecting and measuring NO-dependent angiogenesis in a mouse model. This technique showed strong abdominal neovascularization in wild-type mice, but not eNOS knockout mice, locally injected with VEGF, as well as stimulation of angiogenesis in NO donor-injected mice. This technique also revealed the inhibitory effect of the NOS inhibitor N(G)-iminoethyl-L-ornithine in VEGF-mediated in vivo angiogenesis. This chapter describes intravital microscopy as a new imaging technique for detecting NO-dependent angiogenesis in an animal model.

Clinical analysis of synchronous primary neoplasms of the female reproductive tract.

OBJECTIVES: In this study, a histopathologic review of synchronous primary neoplasms including gynecologic malignancies is presented, and the possible correlation among discrete tumor subsets, natural history, and survival is evaluated. METHODS: Between the years 2000 and 2005, 20 patients suffering from synchronous primary cancers of gynecologic malignancy were identified. Clinical and pathologic information was obtained from medical records. Kaplan-Meier survival analyses were conducted. RESULTS: Patients with synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasm was ovarian cancer coexistent with endometrial cancer (40%). The mean age of patients suffering from synchronous ovarian and endometrial cancer was 45.2 years. All patients with synchronous primary genital malignancies underwent hysterectomy with bilateral salpingo-oophorectomy and/or adjuvant therapy. The mean duration of survival was 57 months (S.E.: 10.0; 95% confidence interval: 37-77). CONCLUSION: Patients suffering from primary genital malignancies are sometimes co-afflicted with other primary cancers. Synchronous ovarian and endometrial cancer constitutes the most common of these cases, and is detected at a relatively early age, with generally favorable prognoses.