Yehuda Ullmann

Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice.

Alopecia areata is a tissue-restricted autoimmune disease of the hair follicle, which results in hair loss and baldness. It is often psychologically devastating. The role of T lymphocytes in this disorder was investigated with cell transfer experiments. Scalp explants from patients were transplanted to severe combined immunodeficiency (SCID) mice and injected with autologous T lymphocytes isolated from involved scalp. T lymphocytes which had been cultured with hair follicle homogenate along with antigen-presenting cells were capable of inducing the changes of alopecia areata, including hair loss and perifollicular infiltrates of T cells, along with HLA-DR and ICAM-1 expression of the follicular epithelium. Similar changes were not noted in grafts injected with scalp-derived T cells that had not been cultured with follicular homogenate. These data indicate that alopecia areata is mediated by T cells which recognize a follicular autoantigen.

Enhancing the survival of aspirated human fat injected into nude mice

Injection of aspirated fat is now the most commonly used technique for the filling of depressed areas. Partial absorption of the injected fat is the main limitation of this procedure. Cariel T.M. is an enriched serum-free cell culture medium, its ability to enhance the survival of human aspirated fat grafts was investigated in the nude mouse model. A volume of 0.75-cc Cariel preprocessed fat was injected under the scalp skin of 16 nude mice in the experimental group, and the same volume of saline preprocessed fat was injected to 15 control group of mice. Significant maintenance of the weight, 46 percent in the experimental group compared with 29 percent in the control group (p < 0.008), and the volume, 44 percent in the experimental group compared with 31 percent in the control group (p < 0.026), was observed, after 15 weeks, in this newly used model. It seems that addition of the nutrients enriched with anabolic hormones enabled the survival and take of more adipose cells in the graft.

Aloe vera gel hindered wound healing of experimental second-degree burns: a quantitative controlled study.

In the present study, Aloe vera gel (AVG) was applied to experimental second-degree burns in guinea pigs, and its effects on epithelialization, wound contraction, newly formed granulation tissue, and regeneration of hair follicles was compared with that effected by 1% silver sulfadiazine cream (AgSD). Epithelialization (%mean +/- SEM) on postburn day 8, 16, and 24 of the AVG-treated wounds was 38.72% +/- 2.71%, 60.34% +/- 3.28%, and 92.46% +/- 2.26%, respectively, while that of the AgSD-treated burns was 53.35% +/- 2.65%, 94.84% +/- 2.65%, and 100%, respectively (P less than .001). Contraction of the AVG-wounds was significantly higher than that of the AgSD-treated burns during 24 days of the study (P less than .001). The thickness of the newly formed granulation tissue was higher in the AVG-treated wounds (P less than .001), while the hair follicles count was significantly lower (P less than .001) compared with the AgSD-treated burns. It is concluded that this preparation of Aloe vera gel hindered the healing process of the present burn wound model when compared with 1% silver sulfadiazine cream.

Topical Erythropoietin Promotes Wound Repair in Diabetic Rats

Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

The Effect of Interleukin-8 on the Viability of Injected Adipose Tissue in Nude Mice

Adipose tissue injection as a free graft for the correction of soft-tissue defects is a widespread procedure in plastic surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study was to improve the viability of the injected fat by the use of interleukin-8. The rationale for the use of interleukin-8 was its abilities to accelerate angiogenesis and attract inflammatory cells and fibroblasts, providing the injected adipocytes more feeding vessels and a well-established graft bed to enhance their viability. Human adipose tissue, obtained by suction-assisted lipectomy, was re-injected into the subcutis in the scalp of nude mice. Interleukin-8 (0.25 ng) was injected subcutaneously to the scalp as a preparation of the recipient site 24 hours before the fat injection and was added to the fat graft itself (25 ng per 1 cc of injected fat). In the control group, pure fat without interleukin-8 was injected and no interleukin-8 was added for the preparation of the recipient site. One cubic centimeter of fat was injected in each animal in both the study and control groups. There were 10 animals in each group. The animals were euthanized 15 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. In addition, triglyceride content and adipose cell sizes were measured as parameters for fat cells viability. Histologic analysis demonstrated significantly less cyst formation in the group treated with interleukin-8. No significant differences were found between the groups with regard to graft weight and volume or the other histologic parameters investigated. No significant differences were demonstrated in adipose cell sizes and their triglyceride content. In conclusion, less cyst formation, indicating improved quality of the injected fat, can be obtained by the addition of interleukin-8. Further studies of various dosages of interleukin-8 and their long-term effect are required before these encouraging results could be applied clinically.

Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

Background Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

Ageing of human epidermis: the role of apoptosis, Fas and telomerase

Background  Aged human epidermis is characterized by morphological changes including flattening of the dermal–epidermal junction and a decrease in thickness.

The revised "reconstructive ladder" and its applications for high-energy injuries to the extremities.

In this report, we tried to evaluate the merits of the classic “reconstructive ladder” and other reconstructive tools, such as acute shortening followed by distraction osteogenesis and a vacuum-assisted closure device, for the treatment of high-energy injuries. Thirty-seven patients suffering from high-velocity injuries to the extremities caused by war weapons and blast terror attacks were treated at our institution. The fractures were initially stabilized by the Association for the Study of Internal Fixation (AO/ASIF) unilateral tubular external fixator, which was changed 2–3 days later to a circular Ilizarov frame for 19 patients. Temporary acute shortening was performed for 5 patients. Skin grafts were performed for 21 patients, local or regional flaps for 14 patients, and free flaps for 6. Vacuum-assisted closure was selected for 8 patients. The wounds were successfully closed in all the patients. Two patients with upper-limb injuries had nonunion. Motor nerve injuries recovered in 7/10 patients. Due to hypergranulating tissue, 2 patients treated with vacuum-assisted closure (VAC) had to stop treatment early. Their wounds were closed with skin graft or local flap. The classic reconstructive ladder, starting from direct closure and ending with a free flap, should be extended for limb traumas and include acute shortening with or without angulation, followed by distraction osteogenesis and the VAC system on the same step as the free flap.

The Beneficial Effect of Blocking Kv1.3 in the Psoriasiform SCID Mouse Model

The Kv1.3 channel is important in the activation and function of effector memory T cells. Recently, specific blockers of the Kv1.3 channel have been developed as a potential therapeutic option for diverse autoimmune diseases. In psoriatic lesions, most lymphocytes are memory effector T cells. The aim of the present study was to detect the expression of Kv1.3 channels in these cells in psoriatic lesions as well as in human psoriasiform skin grafts using the severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemical staining for Kv1.3 expression and various inflammatory markers was performed in sections obtained from six psoriatic patients and 18 beige-SCID mice with psoriasiform human skin grafts. Six grafted mice were treated with Stichodactyla helianthus neurotoxin (ShK), a known Kv1.3 blocker. The results showed an increased number of Kv1.3+ cells in the psoriatic skin as well as in the psoriasiform skin grafts as compared with normal skin and normal skin grafts. Injections of ShK showed a marked therapeutic effect in three of six psoriasiform skin grafts. A significantly decreased number of Kv1.3+ cells was observed in the responders compared with the control grafts. This pilot study, although performed in a small number of mice, reveals the possible beneficial effect of Kv1.3 blockers in psoriasis patients.

A Side-by-side Prospective Study of Intense Pulsed Light and Nd:yag Laser Treatment for Vascular Lesions

Recently, lasers and light systems are used more for the treatment of vascular lesions due to their noninvasiveness, ease of use, and short recovery time. This side-by-side prospective study compares results, satisfaction, and complications after intense pulsed light (IPL) and Nd:Yag laser treatment of small vascular lesions. Twenty-five patients with telangiectases, leg veins, or cherry angiomas underwent treatment of the same category of lesion in the same area. One year after completing treatment, patients were asked to report their satisfaction level after comparing digital photos before and after treatment; 72% felt they had good to excellent results after Nd:Yag treatment, while only 48% felt the same after IPL. The most common side effect after Nd:Yag was hyperpigmentation. Satisfaction level was significantly higher after Nd:Yag than after IPL. Patients with telangiectases, cherry angiomas, or leg veins <1 mm were more satisfied after IPL, while those with leg veins >1 mm were more satisfied after Nd:Yag. Overall, satisfaction with treatment of vascular lesions was greater with Nd:Yag although this method was more painful.