Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

Combined millimeter wave and cyclophosphamide therapy of an experimental murine melanoma

The objective of the present studies was to investigate whether millimeter wave (MMW) therapy can increase the efficacy of cyclophosphamide (CPA), a commonly used anti-cancer drug. The effect of combined MMW-CPA treatment on melanoma growth was compared to CPA treatment alone in a murine model. MMWs were produced with a Russian made YAV-1 generator. The device produced 42.2 +/- 0.2 GHz modulated wave radiation through a 10 x 20 mm rectangular output horn. The animals, SKH-1 hairless female mice, were irradiated on the nasal area. Peak SAR and incident power density were measured as 730 +/- 100 W/kg and 36.5 +/- 5 mW/cm2, respectively. The maximum skin surface temperature elevation measured at the end of 30 min irradiation was 1.5 degrees C. B16F10 melanoma cells (0.2 x 10(6)) were implanted subcutaneously into the left flank of mice on day 1 of the experiment. On days 4-8, CPA was administered intraperitoneally (30 mg/kg/day). MMW irradiation was applied concurrently with, prior to or following CPA administration. A significant reduction (P < .05) in tumor growth was observed with CPA treatment, but MMW irradiation did not provide additional therapeutic benefit as compared to CPA alone. Similar results were obtained when MMW irradiation was applied both prior to and following CPA treatment.     

Localized tenosynovial giant cell tumor of tendon sheath. A case report

BACKGROUND: Localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) is a benign, slowly growing lesion with a peak incidence in the third to fifth decade of life. It is thought to arise from the synovium of tendon sheaths, frequently affecting interphalangeal joints of the hands, feet, ankles and knees. Although the histopathologic appearances are well established, only a few reports describe the cytomorphology of this lesion. CASE: A 37-year-old female presented with a slowly growing, nontender mass located near the left ankle joint. The cytologic features of localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) include abundant mononuclear histiocytic cells occurring singly and in three-dimensional tissue fragments, hemosiderin within histiocytes and a few multinucleated giant cells. Subsequently, the histopathologic examination of the surgical specimen was proven to be TGCT-L. CONCLUSION: Fine needle aspiration cytology can be used as a diagnostic tool for early and accurate detection of TGCT-L since the cytologic features combined with clinical details are sufficiently distinctive.     

Actions of Ginkgo Biloba related to potential utility for the treatment of conditions involving cerebral hypoxia

Neuronal hypoxia results from a variety of cerebrovascular accidents or 'normal' age-associated anatomic changes. The consequences vary from mild deficits in neurologic function to massive neuropathology. Present pharmacotherapeutic therapy is not ideal. Two apparently disparate approaches to the search for better treatment or prevention-one involving reassessment of herbal remedies as 'alternative' medicine and the other one involving the desirability of increased structural diversity in HTS (high-throughput screening) libraries and as combinatorial chemistry templates-have converged in a rekindling of interest and a reevaluation of the pharmacologic properties of substances such as extract from the leaves of Ginkgo biloba Linne (form. Salisburia adiantifolia Sm.). There are reports of positive results from a small number of controlled clinical trials (albeit with small numbers of patients) sufficient to suggest that 'Ginkgo' might have therapeutic benefit in some situations or subset of patients. The pharmacologic mechanism by which Ginkgo might be able to provide the observed effect is not clear. However, it is believed that the flavonoid and terpenoid components of Ginkgo extract might produce beneficial therapeutic effects through mechanisms acting separately or in concert, such as the antagonism of PAF (platelet activating factor), antioxidant and metabolic actions, and effects on neurotransmitters. These mechanisms are reviewed in this article.     

Millimeter wave dosimetry of human skin

To identify the mechanisms of biological effects of mm waves it is important to develop accurate methods for evaluating absorption and penetration depth of mm waves in the epidermis and dermis. The main characteristics of mm wave skin dosimetry were calculated using a homogeneous unilayer model and two multilayer models of skin. These characteristics included reflection, power density (PD), penetration depth (delta), and specific absorption rate (SAR). The parameters of the models were found from fitting the models to the experimental data obtained from measurements of mm wave reflection from human skin. The forearm and palm data were used to model the skin with thin and thick stratum corneum (SC), respectively. The thin SC produced little influence on the interaction of mm waves with skin. On the contrary, the thick SC in the palm played the role of a matching layer and significantly reduced reflection. In addition, the palmar skin manifested a broad peak in reflection within the 83-277 GHz range. The viable epidermis plus dermis, containing a large amount of free water, greatly attenuated mm wave energy. Therefore, the deeper fat layer had little effect on the PD and SAR profiles. We observed the appearance of a moderate SAR peak in the therapeutic frequency range (42-62 GHz) within the skin at a depth of 0.3-0.4 mm. Millimeter waves penetrate into the human skin deep enough (delta = 0.65 mm at 42 GHz) to affect most skin structures located in the epidermis and dermis.     

Triester wax: a novel neutral lipid from the skin of the rhino mutant mouse.

A novel class of neutral lipids has been isolated from the skin of the rhino mutant mouse and has been characterized as a triester wax. The lipid, on saponification and transesterification, yielded fatty acids, omega-hydroxy fatty acids and 1,2-alkane diols. These products were identified by gas-liquid and thin-layer chromatography, infrared, nuclear magnetic resonance and mass spectroscopy, combined gas-liquid chromatography and mass spectrometry and chemical methods. Fatty acids were found to be predominantly of even chain length between C14 and C36 with highest concentration at C22 : 1. Hydroxy fatty acid methyl esters (trimethylsilyl ether derivatives) showed the presence of only three components in the relative abundance of 9: 70 : 21. The structure of the major component was established as 34-hydroxytetratricont-25-enoic acid and the other two components were characterized as 32-hydroxyditricont-23-enoic and 36-hydroxyhexatricont-27-enoic acids. In addition to these omega-9 unsaturates, other isomers having unsaturation at omega-7 and omega-8 were also present in small amounts. The 1,2-alkane diols were predominantly saturated in the range of C16-C24.     

Effect of cyclophosphamide and 61.22 GHz millimeter waves on T-cell, B-cell, and macrophage functions

The present study was undertaken to investigate whether millimeter waves (MMWs) at 61.22 GHz can modulate the effect of cyclophosphamide (CPA), an anti-cancer drug, on the immune functions of mice. During the exposure each mouse's nose was placed in front of the center of the antenna aperture (1.5 x 1.5 cm) of MMW generator. The device produced 61.22 +/- 0.2 GHz wave radiation. Spatial peak Specific Absorption Rate (SAR) at the skin surface and spatial peak incident power density were measured as 885 +/- 100 W/kg and 31 +/- 5 mW/cm(2), respectively. Duration of the exposure was 30 min each day for 3 consecutive days. The maximum temperature elevation at the tip of the nose, measured at the end of 30 min, was 1 degrees C. CPA injection (100 mg/kg) was given intraperitoneally on the second day of exposure to MMWs. The animals were sacrificed 2, 5, and 7 days after CPA administration. MMW exposure caused upregulation in tumor necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages suppressed by CPA administration. MMWs also caused a significant increase in interferon-gamma (IFN-gamma) production by splenocytes and enhanced proliferative activity of T-cells. Conversely, no changes were observed in interleukin-10 (IL-10) level and B-cell proliferation. These results suggest that MMWs accelerate the recovery process selectively through a T-cell-mediated immune response.     

Iron and iron/manganese ratio in forage from Icelandic sheep farms: relation to scrapie

This study was undertaken in order to examine whether any connection existed between the amounts of iron in forage and the sporadic occurrence of scrapie observed in certain parts of Iceland. As iron and manganese are considered antagonistic in plants, calculation of the Fe/Mn ratios was also included by using results from Mn determination earlier performed in the same samples. Forage samples (n = 170) from the summer harvests of 2001–2003, were collected from 47 farms for iron and manganese analysis. The farms were divided into four categories: 1. Scrapie-free farms in scrapie-free areas (n = 9); 2. Scrapie-free farms in scrapie-afflicted areas (n = 17); 3. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms) (n = 12); 4. Scrapie-afflicted farms (n = 9). Farms in categories 1 and 2 are collectively referred to as scrapie-free farms. The mean iron concentration in forage samples from scrapie-afflicted farms was significantly higher than in forage samples from farms in the other scrapie categories (P = 0.001). The mean Fe/Mn ratio in forage from scrapie-afflicted farms was significantly higher than in forage from scrapie-free and scrapie-prone farms (P < 0.001). The results indicated relative dominance of iron over manganese in forage from scrapie-afflicted farms as compared to farms in the other categories. Thus thorough knowledge of iron, along with manganese, in soil and vegetation on sheep farms could be a pivot in studies on sporadic scrapie.