When Barry Marshall drank a broth of Helicobacter pylori in the mid-1980s, he hoped to prove that the bacteria cause gastric ulcers, a common complaint worldwide. Sure enough, Marshall, then at the Royal Perth Hospital in Western Australia, soon developed gastritis, the precursor to stomach ulcers and gastric cancer. In addition to earning him the 2005 Nobel Prize in Physiology or Medicine with his colleague Robin Warren, this unorthodox—and now infamous—experiment proved that a bacteria caused a chronic disease that had previously been attributed to genetic and lifestyle factors. During the same period, researchers have proposed bacterial and viral triggers for many other chronic diseases, such as cancers and coronary heart disease. But Marshall and Warren's discovery has far wider implications than curing a single disease. "Human microecology is changing, and these changes have manifestations in terms of disease," said Martin Blaser, Chair of the Department of Medicine at New York University (NY, USA). To understand the impact of these changes, researchers need to take a closer look at host–pathogen interactions—both good and bad.

"What's interesting about Helicobacter is that everybody is focusing on its pathogenic role and not enough on its role as an indigenous organism," Blaser said. He thinks that the microbes that live inside humans are not there accidentally—over the course of human history, they have adapted to humans and have made trade-offs to become obligate parasites. As a result, their evolution is inextricably linked to human evolution, as well as to human disease. "Our microbes are a part of human physiology... as much a part... as our liver, or our kidneys, or our heart," Blaser commented. "They are a metabolic compartment or a series of metabolic compartments in the human body and how they behave and... their characteristics are relevant to health and disease."

PURPOSE. To understand the mechanisms mediating retinal ganglion cell loss in glaucoma, the gene expression patterns were compared for transferrin, ceruloplasmin, and ferritin between normal and glaucomatous retina in monkey and human eyes.

METHODS. Laser photocoagulation was used to produce unilateral experimental glaucoma in monkeys. Gene expression was assessed by in situ hybridization and quantitative reverse transcription polymerase chain reaction (PCR). Immunohistochemistry was used to examine the retinal expression of iron-related proteins in the retina in experimental monkey glaucoma and human glaucoma.

RESULTS. Comparison of glaucomatous with control monkey retinas demonstrated increased mRNA expression of transferrin, ceruloplasmin, and ferritin heavy and light chains. In situ hybridization localized retinal gene expression of transferrin mainly to the inner nuclear layer and ferritin to both the inner and outer nuclear layers. Immunohistochemical examination of monkey and human glaucoma for these iron-related proteins demonstrated increases at the protein level.

CONCLUSIONS. Increased mRNA and protein levels of the iron-regulating proteins transferrin, ceruloplasmin, and ferritin are present in glaucoma. Together, these results suggest the involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.

 

Blackfoot disease is an endemic arsenic-induced peripheral vascular disease in southern Taiwan. The main pathologic feature is atherosclerosis, which may relate to imbalances of the adrenergic system. The purpose of this study is to investigate the peripheral adrenergic responses of patients with blackfoot disease. Eight patients with blackfoot disease and four age-matched healthy controls were enrolled in this study. Baseline cutaneous perfusion was measured with a laser Doppler flowmeter. The response of alpha-adrenoceptors in the cutaneous microcirculation was assessed with laser Doppler flowmetry with iontophoresis of phenylephrine into the nailfold. In vitro binding with 125I-cyanopindolol determined beta-adrenoceptor density in lymphocytes.

The cyclic adenosine monophosphate (cAMP) level at baseline and after isoproterenol stimulation reflects lymphocyte beta-adrenergic responsiveness. Results revealed persistently decreased skin perfusion in patients with blackfoot disease. In contrast, there was a transient decrease in skin perfusion in healthy controls after iontophoresis of phenylephrine. Both beta-2 receptor density and isoproterenol-stimulated cAMP levels in lymphocytes decreased. Increased peripheral alpha-adrenergic response and decreased beta-2—adrenergic response are related to increased vascular tone and result in atherosclerosis. Our findings of accentuated alpha-adrenergic response in microcirculation and decreased lymphocyte beta-2—adrenoceptor response play an important role in the pathogenesis of atherosclerosis in blackfoot disease.

Background. To date, a variety of lasers have been used for treating vascular skin lesions. Intense pulsed light (IPL) is a proven technology for vascular lesion management, such as rosacea.

Objectives. The aim of this study was to test the effectiveness of IPL in treating vascular facial lesions in rosacea patients.

Methods. Sixty patients presenting with telangiectasia owing to facial rosacea were selected randomly from the patient population in the Department of Laser Therapy at the Medical Centre Maastricht, the Netherlands. Patients of various skin types (Fitzpatrick I–IV) were selected with an average age of 44.2 years. Five hundred eight sites were treated, with a mean of 4.1 treatments per site and an IPL spectrum ranging from 515 to 1,200 nm with different pulse durations between 4.3 and 6.5 milliseconds. The energy density varied from 25 to 35 J/cm².

Results. Patients were assessed clinically and photographically. A mean clearance of 77.8% was achieved and was maintained for a follow-up period averaging 51.6 months (range 12–99 months). No correlation was found between the clearance of rosacea and patient-related or technical data. For approximately 3 years post-treatment, lesion recurrence was noted in 4 of the 508 treated facial sites.

Discussion. This study demonstrated that IPL treatment of facial rosacea is effective in obtaining clearance of 77.8%, with minimal side effects, and that treatment effects are maintained.

Conclusion. The IPL system, with its broad range of technical variables, is an effective tool in achieving meaningful and lasting rosacea clearance.

Background Persistent erythema and dysesthetic symptoms are typical manifestations of rosacea.

Objective We sought to assess improvement in erythema, symptoms, and quality of life after pulsed dye laser treatment.

Methods Sixteen patients with erythematotelangiectatic rosacea participated. Spectrophotometric erythema measurements were taken from the right and left malar prominence; chin; and nasal alae, dorsum, and tip. A questionnaire rating the Dermatology Life Quality Index and symptoms of flushing, burning, itching, dryness, swelling, and skin sensitivity was completed. Treatment was undertaken with the pulsed dye laser at purpuragenic fluences. Measurements and treatment were repeated at 8-week intervals for a total of two treatments.

Results A statistically significant improvement was observed in symptoms, quality-of-life score, and erythema in all areas with the exception of erythema of the left nasal ala.

Conclusions Pulsed dye laser treatment at purpuragenic fluences is a safe and effective treatment for symptomatic rosacea, resulting in a significant improvement in erythema, symptoms, and quality of life.

Background. Granuloma annulare is a chronic asymptomatic dermatosis that is typically manifested by annular papules arising on the dorsa of the hands, feet, elbows, and knees. Multiple treatment modalities have been used with variable efficacy, but no known cure exists. Obtaining long-term resolution of involved areas is often a therapeutic challenge.

Objective. We report the results of treatment of a patient with localized erythematous granuloma annulare with a 585 nm flashlamp-pumped pulsed dye laser.

Methods. A single granuloma annulare plaque present on the left wrist for 3 years was treated on three occasions with a 585 nm flashlamp-pumped pulsed dye laser initially and repeated at months 5 and 13.

Results. After initial pulsed dye laser treatment, significant flattening and reduction of erythema were evident within the treated area. After a second treatment at month 5 and a third treatment at month 13, further improvement was evident, and long-term remission was achieved.

Conclusion. Localized granuloma annulare may be difficult to manage, presenting a therapeutic challenge. Thorough understanding of available treatment options, their relative efficacies, and risks of complication can facilitate successful management of this chronic disease. Pulsed dye laser therapy may be an effective and relatively safe treatment option for erythematous granuloma annulare, although prospective studies in additional patients would be desirable. Improvement of the condition in a single patient does not imply that others might improve, and variability in response is more likely.

Many lasers have claimed the clinical efficacy on skin rejuvenation. Generally, there are two main laser effects consistent with clinical applications. Systematic and comparative studies are needed to compare different laser effects and probe into the mechanism of laser skin rejuvenation. To conduct a comparative study of collagen remodeling with two different laser effects on mice model in vivo. After depilation, the back skin of KM mice was used for the study. The 1064 nm Q-switched (5 ns) and long-pulsed (0.3 ms) Nd:YAG lasers were applied based on optimal tissue reaction fluence test to irradiate one side of the mice back and leave the other side as the control. Then the collagen remodelling were evaluated at 0, 1, 7, 21, 30 and 60 days, with biophysical parameters' measurements, histological and biochemical examination.

The two lasers applied showed statistical improvements in skin elasticity, dermal thickness and synthesis of hydroxyproline compared with their own controls. Between the two lasers, the Q-switched 1064-nm laser resulted in greater improvements than that of the long-pulsed 1064-nm laser after two months of treatments. Collagen type III increased markedly after the Q-switched 1064-nm laser treatment whereas more collagen type I was elicited by the long-pulsed 1064-nm laser. Q-switched 1064-nm laser was more effective in collagen remodeling compared with long-pulsed 1064-nm laser. Photo-mechanic reaction can cause more synthesis of collagen type III whereas the photo-thermal effect is in favor of formation of collagen type I.

Background: Lasers have been used in the treatment of hypertrophic scars and keloids for more than 20 years. Different laser systems have been examined; among them pulsed dye lasers are currently considered the laser of choice in these settings.

Objectives: The purpose of this study is to review the pertinent literature and provide updated information on different laser therapies available for treatment of keloids and hypertrophic scars.

Methods: A Medline literature search was performed for relevant publications.

Results: In this review the results of published studies in the treatment and prevention of hypertrophic scars and keloids are presented. Suggested mechanisms of action are reviewed. A review of the optimal laser parameters to modulate treatment outcome will be discussed. Different lasers are effective in not only the treatment but also the prevention of hypertrophic scars and keloids, among them PDL is more promising. Most of the suggested theories are based on the selective photothermolysis in which the light energy emitted from a vascular laser is absorbed by hemoglobin, generating heat and leading to coagulation necrosis, neocollagenesis, collagen fiber heating with dissociation of disulfide bonds and subsequent collagen fiber realignment.

Conclusion: The optimal laser is currently 585 nm PDL, although the recent results of Q-switched 532 nm frequency-doubled Nd:YAG are promising. Early use of lasers are beneficial, especially in those who are prone to develop these lesions.

Background and Objectives Striae distensae are dermal scars with flattening and atrophy of the epidermis. Successful treatment of these stretch marks has been disappointing. The non-ablative 1,450-nm diode laser has been shown to improve atrophic scars and may be expected to improve striae. As yet, no study has been published to document the effects of this laser on striae. Our aim is to evaluate the efficacy of the 1,450-nm diode laser in the treatment of striae rubra and striae alba in Asian patients with skin types 4-6.

Study Design/Materials and Methods  Striae on one half of the body in 11 patients were treated with the 1,450-nm diode laser with cryogen cooling spray with the other half serving as a control. The following parameters were used: 6 mm spot size and dynamic cooling device (DCD) for 40 milliseconds to protect the epidermis. Patients were randomly assigned to receive either 4, 8, or 12 J/cm2. A total of three treatments were given at 6-week intervals. The following sites were treated: abdomen, arms, back, buttocks, and thighs. Two patients had striae rubra and nine striae alba. Clinical photographs were taken before and after each treatment and analysis was undertaken through photographic evaluation by non-treating physicians.

Results At 2 months after the last treatment, no patients showed any noticeable improvement in the striae on the treated side compared to baseline and to the control areas. Side effects were limited to transient erythema and postinflammatory hyperpigmentation (PIH), which occurred in seven (64%) patients.

Conclusions The non-ablative 1,450-nm diode laser is not useful in the treatment of striae in patients with skin types 4, 5, and 6. Lasers Surg. Med. 38:196-199, 2006. © 2006 Wiley-Liss, Inc.

Background: Millisecond-pulsed Nd:YAG lasers have been developed for the treatment of reticular leg veins.

Objective: We evaluated the effectiveness of a single treatment with a 50 millisecond 1064 nm Nd:YAG laser in the treatment of reticular veins of the lower extremity.

Methods: Twenty patients with reticular veins measuring 1.0 to 3.0 mm in diameter received one treatment with a 1064 nm Nd:YAG laser (Coolglide, Altus, Burlingame, Calif) at fluences of 100 J/cm² and 50 millisecond pulse duration. Symmetric matched areas that were left untreated served as the control. Eleven patients were pretreated with a topical anesthetic cream for 1 hour before treatment and wore compression stockings for 5 days after treatment. Nine patients were treated without topical anesthesia and did not wear compression stockings. Percent clearing and side effects were determined by 3 nontreating physicians (at each respective site) comparing projected Kodachrome images 1 month and 3 months after treatment. Patients also performed a self-assessment of their results.

Results: Two-thirds of vessels measuring 1 to 3 mm in diameter cleared more than 75% with one treatment. Larger vessels appeared to improve more than smaller vessels. Immediate treatment discomfort was tolerable. Side effects were minimal and included superficial thrombosis, delayed bruising, hyperpigmentation, and matting. Conclusion: Millisecond-pulsed Nd:YAG lasers used with 50 millisecond pulses are effective in the treatment of reticular leg veins. (J Am Acad Dermatol 2003;48:76-81.)

Background and Objective. A comparative overview is presented, both theoretical and clinical, for intense pulsed light (IPL) and laser treatment of facial telangiectasias and pigmented lesions.

Materials and Methods. A narrative approach describes light penetration into the epidermis, dermis, dermal-epidermal junction, and facial ectasias. Based on mathematical models, we examine some temperature profiles for monochromatic and broadband light sources. Specifically, temperature elevations of representative vascular targets are discussed. Also, clinical scenarios are reviewed for both IPL and laser. Although multiple monochromatic devices are reviewed, only the 532 and 595 nm wavelengths are emphasized.

Results. In theory, an IPL can be filtered to simulate 532 and 595 nm laser light in the treatment of telangiectasias and dyschromias. In comparing our experiences with the different devices, all three (IPL, 532 nm laser, and 595 nm laser) are capable of achieving a reduction in ectasias and hyperpigmented macules.

Conclusions. With an optimal set of parameters, IPLs and lasers are comparable in the treatment of vascular and pigmented lesions with respect to treatment efficiency and safety.

Begoña Comín-Anduix, László G. Boros§, Silvia Marin, Joan Boren, Carles Callol-Massot, Josep J. Centelles, Josep L. Torres¶, Neus Agell, Sara Bassilian§, and Marta Cascante
From the Department of Biochemistry and Molecular Biology, CeRQT-PCB at Barcelona Scientific Park, University of Barcelona, 1 Martí i Franquès, Barcelona 08028, Spain, the § Harbor-UCLA Research and Education Institute, University of California, Los Angeles, School of Medicine, Torrance, California 90502, the ¶ Department of Peptide and Protein Chemistry, Institute for Chemical and Environmental Research (IIQAB-CSIC), C/Jordi Girona 18-26, 08034-Barcelona, Spain, and the  Department of Cell Biology, IDIBAPS, Faculty of Medicine, University of Barcelona, Casanova 143, E-08036, Barcelona, Spain

The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC50 concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G1 peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased 13C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC50 (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.

OBJECTIVE: To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease.

 PATIENTS AND METHODS: Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days.

 Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion.

  RESULTS: Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period.

 In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P less than .04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P less than .002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P less than .005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P less than .001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P less than .05). CONCLUSION: In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.