Keratinocyte conditioned medium abrogates the modulatory effects of IGF-1 and TGF-β1 on collagenase expression in dermal fibroblasts

Overexpression of wound healing-promoting factors such as transforming growth factor-1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) during the healing process has been implicated in the development of dermal fibrosis in patients following thermal injury, surgical incision, and deep trauma. However, the mechanism through which the expression of these two fibrogenic factors is slowed down and/or abrogated in the late stages of the healing process is not known. Here, we hypothesize that keratinocyte-releasable factors counteract the fibrogenic role of both IGF-1 and TGF-beta1 in fibroblasts. To test this hypothesis, the levels of collagenase (MMP-1), as an index for extracellular matrix degradation, in dermal fibroblasts in response to either keratinocyte-conditioned medium (KCM) or our recently identified keratinocyte-releasable stratifin in the presence and absence of either IGF-1, TGF-beta1, or both were evaluated. The results of Northern analysis showed a significant increase in collagenase mRNA expression in cells treated with KCM in the presence of both IGF-1 and TGF-beta1. The effect was, at least in part, due to keratinocyte-derived stratifin that was present in KCM. This was ascertained as the levels of MMP-1 mRNA were markedly reduced when cells were treated with stratifin-immuno-depleted KCM. The results of Western blot analysis showed an increase in the level of MMP-1 protein in stratifin-treated fibroblasts and this was consistent with the level of MMP-1 mRNA expression detected by Northern analysis. However, in contrast to KCM, whose efficacy on MMP-1 expression was modestly reduced by either IGF-1 and TGF-beta1, or a combination of both, these factors abrogated the MMP-1 stimulatory effect of stratifin in fibroblasts. In summary, the results of this study revealed that both stratifin and KCM stimulate the expression of MMP-1-in fibroblasts and this effect can be abrogated by either IGF-1, TGF-beta1, or a combination of both.     

Trisomy 20q13 --> 20qter in a girl with multiple congenital malformations and a recombinant chromosome 20 inherited from a paternal inversion (20)(p13q13.1): clinical report and review of the trisomy 20q phenotype

We report on a patient with a rec(20)dup(20q) chromosome abnormality derived from a paternal chromosome 20 inversion [inv(20)(p13q13.1)]. The rearrangement results in a duplication of 20q13.1 to 20qter and a deletion of 20p13 to 20pter. The patient is a girl with craniofacial features and multiple congenital malformations that overlap with the abnormalities previously described in trisomy 20q syndrome. To our knowledge this is the first report of a patient with rec(20)dup 20q.     

Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its effects in biochemical responses

1. Laboratory experiments were carried out to assess uptake and metabolism of the epilepsy drug, carbamazepine and its consequent biological responses in marine clam (Ruditapes decussatus) a model non-target organism in ecotoxicology.

2. Clams were exposed to two nominal concentrations (C1?=?30?μg/L and C2?=?50?μg/L) of CBZ for a maximum period of 14 days. Analysis of CBZ and their metabolites in clam and water after exposure to two nominal concentrations of the pharmaceutical drug were performed using UPLC-HRMS analysis. CBZ accumulation reached an average tissue concentration of 1241.59 ng/g dw and 1664.33 ng/g dw at low and high nominal concentration, respectively.

3. Furthermore, a metabolite (3-hydroxy-CBZ) was detected in tissues indicating carbamazepine translocation and metabolism inside clam, suspect screening of CBZ glucuronides was also performed by accurate mass extraction but it could not be detected.

4. Activities of antioxidant enzymes superoxide dismutase, catalase and gluthatione-S-transferase generally increased. Change in the contents of glutathione, malondialdehyde and protein carbonyl were also studied.

5. Results indicated that the bioaccumulation of CBZ resulted in the changes of the antioxidant defense system and the production of ROS with the oxidative stress, ultimately induced alteration in lipid peroxidation and protein carbonyl.     

Current knowledge,attitude, and patterns of oral contraceptives utilization among women in Jordan

Background

Studies exploring the knowledge, attitude and patterns of OCs use among women in Jordan are lacking. The aim of this study was to assess knowledge, attitude, and patterns of oral contraceptives (OCs) utilization among women in Jordan.

Methods

A face-to-face questionnaire inquiring demographic information and issues related to knowledge and use of OCs was completed by women (n?=?1571), who have had used OCs at least once in their lifetime. A model was created to assess the effects of knowledge, attitude and previous experience on the patterns of OCs utilization.

Results

Jordanian women exhibited positive attitudes towards OCs efficacy and safety. This positive attitude was approvingly associated with the patterns of use. However, only half of participating women reported that they knew how to use OCs. About 60 % of women received recommendations for OCs use from a physician. Moreover, women’s knowledge about OCs mechanism of action was obtained namely from physician (29.9 %). Side effects were reported in 75.1 % of participating women. Reported side effects were headache (41.2 %), mood swings (35.5 %), irritability (33.5 %) and weight gain (28.7 %). Interestingly, the occurrence of side effects was the main reason for OCs discontinuation.

Conclusion

The study showed that women who have positive attitude toward OCs tend to utilize them more appropriately. However, there is still need for educational programs to enhance knowledge about OCs utilization in Jordan.

     

Demographic, clinical and therapeutic features of adult visceral leishmaniasis at the Rabta hospital in Tunis (tunisia) from 1983 to 2002

The purpose of this study was to evaluate in a retrospective analysis, cases of Mediterranean visceral leishmaniasis (VL) diagnosed in adults during a 20-year period in a department of infectious diseases. Demographic data, clinical and laboratory features and therapeutic findings were considered. During the study period, 22 cases of VL were diagnosed, and 6 (27%) were associated with HIV infection. Fever and splenomegaly were observed in all cases. Anaemia was constant. The anti-leishmanial IF titer was positive among 21 patients (95%). Smears from bone marrow aspiration were positive at microscopy in 95% of cases. Zymodeme analysis was carried out in nine isolates. L. infantum zymodeme MON-1 was characterized in all cases. Seventeen patients (77%) received meglumine antimoniate (MA) (20 mg SbV/kg per day) and 5 (23%) patients amphotericin B (AB) (0.5-1 mg/kg per day) for an average period of 25 days (10-49 days). Adverse events occurred in 7 patients (32%), among them 4 received AB. Clinical cure was achieved with success in 21 patients (95%). After a successful MA treatment of the initial episode, VL relapse was observed in one HIV-positive patient. Only one HIV-positive patient died from neurological disorders. VL is rare in adults. However, its incidence is increasing everywhere in the world, because of HIV-related cases. Its prognosis depends on the precocity of diagnosis and treatment.     

Transdifferentiation of peripheral blood mononuclear cells into epithelial-like cells

Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3varsigma for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3varsigma and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P 相似文献   

Prevalence of lower extremities peripheral arterial disease among Egyptian ischemic patients attending cardiac rehabilitation unit

Background

Atherosclerosis is progressive and diffuse pathological disorders which can simultaneously affect multiple vascular beds. Diagnosing Lower extremities peripheral arterial disease (PAD) in patients with Coronary artery disease (CAD) admitted to cardiac rehabilitation program can help to tailor exercise regimen to fit these patients, in addition, early treatment and/or intervention may help to control progression of the disease.