Derivatives of the self-complementary 2-guanidiniocarbonyl pyrrole 5-carboxylate zwitterion (1) (previously reported by us to dimerize to 1∙1 with an aggregation constant of ca. >1010 M-l in DMSO) aggregate in a diverse manner depending on e.g. variation of concentration or its protonation state. The mode of aggregation was analyzed by spectroscopic (NMR, UV) and microscopic (AFM, SEM, HIM and TEM) methods. Aggregation of dimers of these zwitterions to higher supramolecular structures was achieved by introduction of sec-amide substituents at the 3-position, i.e. at the rearward periphery of the parent binding motif. A butyl amide substituent as in 2b enables the discoid dimers to further aggregate into one-dimensional (rod-like) stacks. Quantitative UV dilution studies showed that this aggregation is strongly cooperative following a nucleation elongation mechanism. The amide hydrogen seems to be essential for this rod-like aggregation, as neither 1 nor a corresponding tert-amide congener 2a form comparable structures. Therefore, a hydrogen bond-assisted π-π-interaction of the dimeric zwitterions is suggested to promote this aggregation mode, which is further affected by the nature of the amide substituent (e.g. steric demand), enabling the formation of bundles of strands or even two-dimensional sheets. By exploiting the zwitterionic nature of the aggregating discoid dimers a reversible pH switch was realized: dimerization of all compounds is suppressed by protonation of the carboxylate moiety, converting the zwitterions into typical cationic amphiphiles. Accordingly, typical nanostructures like vesicles, tubes, and flat sheets are formed reversibly under acidic conditions, which reassemble into the original rod-like aggregates upon readjustment to neutral pH.

BACKGROUND:

Systemic lupus erythematosus (SLE) is associated with a numerical and functional reduction of peripheral blood (PB) invariant natural killer T (iNKT) cells. Limited information exists on the role of iNKT cells in the pathogenesis of lupus erythematosus.

OBJECTIVE:

To investigate the frequency and phenotype of iNKT cells in PB and dermal infiltrates from patients with SLE, subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE).

METHODS:

PB was obtained from 23 SLE, 6 SCLE, and 11 DLE patients, and from 30 healthy controls. iNKT cell frequency and CCR4/CCR6 surface expression were assessed by flow cytometry. The frequency and phenotype of skin infiltrating Vα24(+)Vβ11(+) iNKT cells were investigated by immunofluorescence in lesional biopsies from 20 patients, unaffected skin from 3 patients, and from 6 healthy controls.

RESULTS:

Lupus erythematosus patients displayed significantly lower percentages of circulating CD3(+)6B11(+) iNKT cells compared to healthy controls. Whereas CCR6 expression on iNKT cells was enhanced in active SLE patients regardless of cutaneous involvement compared to healthy controls, CCR4 was exclusively increased in patients with active cutaneous lesions. Furthermore, iNKT cells were significantly enriched in lesional skin of SLE and DLE patients, but not in unaffected skin of lupus patients. The majority of lesional iNKT cells expressed IFN-γ and CCR4.

CONCLUSION:

The deficiency in circulating iNKT cells in cutaneous lupus erythematosus is associated with an increase of iNKT cells at the site of cutaneous inflammation. These data underscore the importance of analyzing iNKT cells not only in PB, but also in the target tissues.

To show a new technique of laparoscopic intracorporeal anastomosis for transrectal bowel resection with transvaginal specimen extraction, a technique particularly suited for treatment of bowel endometriosis.Step-by-step explanation of the technique using videos and pictures (educative video).Endometriosis may affect the bowel in 3% to 37% of all endometriosis cases. Bowel endometriosis affects young women, without any co-morbidities and in particular without any vascular disorders. In addition, affected patients often express a desire for childbearing. Radical excision is sometimes required because of the impossibility of conservative treatment such as shaving, mucosal skinning, or discoid resection. Bowel endometriosis should not be considered a cancer, and consequently maximal resection is not the objective. Rather, the goal would be to achieve functional benefit. As a result, resection must be as economic and cosmetic as possible. The laparoscopic approach has proved its superiority over the open technique, although mini-laparotomy is generally performed to prepare for the anastomosis.Total laparoscopic approach in patients with partial bowel stenosis, using the vagina for specimen extraction.This technique of intracorporeal anastomosis with transvaginal specimen extraction enables a smaller resection and avoidance of abdominal incision enlargement that may cause hernia, infection, or pain. When stenosis is partial, this technique seems particularly suited for treatment of bowel endometriosis requiring resection. If stenosis is complete, the anvil can be inserted above the lesion transvaginally.

Each year, millions of platelet transfusions save the lives of cancer patients and patients with bleeding complications. However, between 10 and 30% of all platelet transfusions are clinically ineffective as measured by corrected count increments, but no test is currently used to identify and avoid these transfusions. ThromboLUX(®) is the first platelet test intended to routinely characterize platelet concentrates prior to transfusion.ThromboLUX is a non-invasive, optical test utilizing dynamic light scattering to characterize a platelet sample by the relative quantity of platelets, microparticles, and other particles present in the sample. ThromboLUX also determines the response of platelets to temperature changes. From this information the ThromboLUX score is calculated. Increasing scores indicate increasing numbers of discoid platelets and fewer microparticles. ThromboLUX uses calibrated polystyrene beads as a quality control standard, and accurately measures the size of the beads at multiple temperatures.Results from apheresis concentrates showed that ThromboLUX can determine the microparticle content in unmodified samples of platelet concentrates which correlates well with the enumeration by flow cytometry. ThromboLUX detection of microparticles and microaggregates was confirmed by microscopy.ThromboLUX provides a comprehensive and novel analysis of platelet samples and has potential as a noninvasive routine test to characterize platelet products to identify and prevent ineffective transfusions.

INTRODUCTION:

The Laotian rock rat is a relict species in a sister group relationship to hystricognath rodents (Hystricognathi). We asked whether there were similarities in placentation that might reflect this relationship or differences that might cast light on the evolution of Hystricognathi.

METHODS:

We examined the reproductive tract of nonpregnant (n = 5), early (n = 3) and mid to late gestation (n = 2) females. Selected characters were mapped to a phylogenetic tree to examine their evolution in rodents.

RESULTS:

The chorionic placenta was discoid and labyrinthine with a spongy zone but without internal lobes. The interhemal region was hemodichorial with syncytiotrophoblast lining maternal blood spaces and an inner layer of vacuolated cytotrophoblast. There was no subplacenta. The yolk sac was well developed with a villous portion that faced the placental disk but no fibrovascular ring. There was a single fetus that very likely would be precocial at birth.

DISCUSSION:

A lobulated labyrinth and the presence of a subplacenta and a fibrovascular ring emerged as synapomorphies for Hystricognathi. Laonastes, Ctenodactylus and stem Hystricognathi all had precocial young, whereas altriciality was the plesiomorphic condition for rodents. A hemomonochorial interhemal region was plesiomorphic for rodents and Hystricognathi, and the hemodichorial condition found in Laonastes, and possibly in Ctenodactylus, was unlike that of any rodent studied to date.

CONCLUSION:

Similar to Hystricognathi, Laonastes bears precocial young, but this species lacks placental adaptations such as the subplacenta, suggesting they were evolved subsequent to a change in reproductive strategy in the common ancestor of Laonastes and Hystricognathi.

Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseases have varying etiologies that need to be addressed in order to effectively treat the dyspigmentation. In this review, we describe and discuss the utility of histology in the diagnostic work of hyperpigmentary disorders, and how, in many cases, it can lead to targeted and more effective therapy. We focus on the most common acquired pigmentary disorders seen in Indian patients as well as a few uncommon diseases with distinctive histological traits. Facial melanoses, including mimickers of melasma, are thoroughly explored. These diseases include lichen planus pigmentosus, discoid lupus erythematosus, drug-induced melanoses, hyperpigmentation due to exogenous substances, acanthosis nigricans, and macular amyloidosis.

Abstract

Background:

Discoid lupus erythematosus (DLE) is restricted to the skin, mostly the face, often chronic and disfiguring. Standard medical therapies include topical corticosteroids and antimalarials.. This is a retrospective long-term follow up of refractory DLE treated with different lasers and intense pulsed light (IPL). Methods and materials: Sixteen patients with histologically confirmed DLE participated in this study. Two men and fourteen women; aged 28-69 years, mean age 54 years, were treated at the laser units of the Departments of Dermatology at the University Hospital of Örebro from 2001 and at Skåne University Hospital in Malmö, Sweden from 1999. Several therapies, including first and second line treatments and even cryo therapy had been used, without response. Many patients had marked scarring. Pulsed dye laser (PDL) and IPL were used with low fluencies.

Results:

Of the patients 14/16 were improved regarding itching, erythema, scaling, scarring and pain. There was a low incidence of scarring as a side effect. Two patients were not satisfied because of long healing time (One patient), post inflammatory hyper pigmentation (One patient).

Conclusion:

IPL and PDL could be an early and safe adjunctive therapy to conventional treatment of DLE in the effort to prevent scarring and disfigurement.

We studied vascular structure of the rabbit placenta, especially on three-dimensional morphological patterns and developmental process. Basic structure of maternal arterial system was re-constructed during day 13-18 of pregnancy, forming main routes for blood supply through the arterial sinuses and radial arteries. Intra-villous spaces were drastically developed showing as branches from the terminal radial arteries. Fetal arterial system was generated accompanied with maternal vascular development, showing characteristic features such as the perforating linear artery, hairpin flexion, and circular anastomoses in the capillaries. From the correlation of maternal and fetal blood currents, gas-exchange style in the rabbit placenta was considered as counter-current and pool mixed patterns. These data demonstrated an original feature for the placental arterial systems in rabbits, which differed from other animals having a property for discoid placenta.

BACKGROUND:

Paediatric cutaneous lupus erythematosus (LE) is uncommon and inadequately described in the literature. Similar to adults, children with cutaneous LE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult cutaneous LE have not been sufficiently described.

OBJECTIVES:

The purpose of this study is to detail the demographic and clinical features of paediatric cutaneous LE and then compare these findings to those reported in the adult literature.

METHODS:

A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE.

RESULTS:

Patients presented with all five major subtypes of cutaneous LE, with some notable differences from adult cutaneous LE and previously published reports of paediatric cutaneous LE. Progression from discoid LE to systemic lupus erythematosus (SLE) did not occur in our cohort. Patients with subacute cutaneous LE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for cutaneous LE in our study was equal prior to puberty and female-predominant in post-pubertal patients.

CONCLUSIONS:

Children with cutaneous LE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute cutaneous LE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit ability to generalize this data and relatively short follow-up intervals. This article is protected by copyright. All rights reserved.

Background:

Discoid lupus erythematosus (DLE) is a cutaneous autoimmune inflammatory disease in which the role of conventional dendritic cells (cDCs) in skin damage has not been evaluated.

Objective:

To evaluate the involvement of cDCs in DLE pathogenesis. Material &

Methods:

Skin biopsies from 42 patients with DLE were embedded in paraffin or placed in culture. The dermis was separated and cell suspensions were characterized by flow cytometry.

Results:

We found an increase in cDCs with inflammatory characteristics in the skin of DLE patients, compared with control skins. Interestingly, cDCs from the DLE patients expressed low levels of the inhibitory molecule PD-L1 and showed a high expression of CCR6, which correlated with disease activity. Increased cellular death was observed in the skin of DLE patients compared with control skin and remarkably we found that damage-associated molecular patterns could be responsible for CCR6 expression on cDCs in the skin.

Conclusions:

Our results indicate the presence of pathogenic CCR6(+) cDCs in the skin lesions of DLE patients, which could result from in situ phenotypic changes.