Caspase 9 is decreased in psoriatic epidermis

Psoriasis is a proliferative and inflammatory disease of the skin. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. Apoptosis is a physiological mechanism of homeostasis and development, and caspases are the executioners of apoptosis. This study reports the immunohistochemical localisation of caspase 9 in psoriatic skin and compares it with that seen in normal, healthy control skin. Skin biopsy specimens of lesions were obtained from 15 patients with plaque type psoriasis vulgaris. The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. Biopsies of healthy skin from 10 age-matched and sex-matched healthy control individuals were also analysed. The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. Counts of caspase 9 positive cells from the epidermis of psoriatic skin lesions were significantly lower than those seen in healthy skin (p<0.05). The caspase 9 immunolabelled perivascular cell counts in the dermis were not statistically significantly different in psoriatic lesions versus normal skin (p>0.05). Psoriatic epidermis contains little of the apoptotic marker, caspase 9. The results of this study are indicative of decreased apoptosis in psoriatic epidermis, and no change in the perivascular area in psoriatic lesions. These findings support the idea that decreased apoptosis is seen in psoriatic epidermal cells. Greater understanding of the nature of the disease may open new avenues for further therapeutic modalities.     

Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma

Objective

Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed.

Methods

To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163⁺ tumor-associated macrophages and Foxp3⁺ regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan–Meier curves were generated; multivariate analysis was undertaken as appropriate.

Results

A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival.

Conclusions

Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma.     

Promoter hypermethylation of the <Emphasis Type="Italic">SFRP2</Emphasis> gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

Background  

We have previously reported that expression of the Wnt antagonist genes SFRP1 and SFRP5 is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether SFRP2 promoter methylation might serve as a potential tumor biomarker.     

Effect of subminimal inhibitory concentrations of three fluoroquinolones on adherence of uropathogenic strains of Escherichia coli

The effect of subinhibitory concentrations (1/2-1/32 x MIC) of ciprofloxacin, ofloxacin and levofloxacin on the adherence of three strains of Escherichia coli (a mannose-resistant haemagglutinating clinical isolate, a non-haemagglutinating clinical isolate and the mannose-resistant haemagglutinating ATCC 25922 strain) were studied. Ciprofloxacin had the lowest MIC values but only the 1/2 MIC concentration inhibited adherence of mannose-resistant haemagglutinating strains after exposure to subMIC values. Significant inhibition of adherence was observed with 1/4 x MIC ofloxacin for both haemagglutinating isolate (27096) and the ATCC strain. Levofloxacin might be more effective and safer than ciprofloxacin and ofloxacin as a long acting fluoroquinolone at subMIC values in patients with UTI.     

Comparison of nickel patch test reactivity in phases of the menstrual cycle

BACKGROUND: In earlier studies, it has been shown that severity of some diseases varies with menstrual cycle. Severity of skin diseases such as atopic dermatitis, lupus erythematosus, infections due to herpes virus, urticaria and acne were also reported to increase in the premenstrual phase. Effect of estradiol on the cellular immune system was investigated and it was found to depress the cellular immune response. In our study, we investigated whether nickel patch test reactivity was different during phases of the menstrual cycle and whether there was an increase in sensitivity to nickel during the premenstrual cycle in nickel-sensitive women. METHODS: The study consisted of 30 women who had a history of nickel sensitivity. Finn Chamber nickel patch test was applied to all 30 women by dividing them into two groups of 15 and applying the test first on days 7-10 and then on days 20-24 of the menstrual cycle or vice versa. RESULTS: The reactions of both the groups on days 20-24 were more severe than those on days 7-10 even though the results were not statistically significant. CONCLUSIONS: Estrogens not only impair the skin barrier but also have a negative impact on the immune system. Estradiol has been proved to suppress cellular immunity. In a few studies conducted to date, the relationship between phases of the menstrual cycle and the severity of patch test reactivity has been examined with equivocal results. In our study, we observed that the presence of reactions due to nickel sensitivity was independent of the phases of the menstrual cycle. Nevertheless, we would like to point out the fact that the reactions seen in the second phase of the menstrual cycle were more severe than those seen in the first phase.     

Prevalence of Cryptosporidium infection in hemodialysis patients

The prevalence of Cryptosporidium infection in patients who are on chronic hemodialysis due to end-stage renal failure is investigated and compared with the incidence in the healthy population. Stool specimens of 74 adult hemodialysis patients treated on an outpatient basis and 50 healthy individuals are examined for Cryptosporidium oocysts by using the modified acid-fast method. While 20.27% (15/74) of patients in the dialysis group had Cryptosporidium oocysts in their stools, none (0/50) of the controls had such an infection (p < 0.001). Ten of 15 patients who had Cryptosporidium oocysts in their stool specimens were asymptomatic and the remaining 5 had diarrhea. Four of these 5 diarrheic patients had Cryptosporidium oocysts in their stools and 1 had both Cryptosporidium oocysts and Giardia trophozoites. Since hemodialysis patients with chronic renal failure are candidates for renal transplantation, general preventive measures against infection must be taken and these patients must be screened for their carrier state before transplantation.     

Complications of varicella in healthy children in Izmir, Turkey

BACKGROUND: The purpose of the paper was to evaluate the indications of hospital admissions and complications of varicella infection in immunologically healthy children. METHODS: Between 1997 and 2001, patient records of children hospitalized due to varicella infection were reviewed. Incidence and clinical spectrum of complications and their distribution related to age and seasonal variations were analyzed. RESULTS: A total of 178 immunocompetent children were hospitalized for varicella complications during the study period. This resulted in a crude incidence of 6.3/100 000 population at risk. All hospital admissions were due to accompanying complications. The majority of complications occurred in preschool-age children with a median age of 3 years. No gender predominance was found. The most frequent complications were infectious complications, which were observed in 79 children (44%). Superinfections of the skin were present in 24 patients. Pneumonia was observed in 59 children: 49 had bacterial, 10 had viral pneumonia. Pyogenic arthritis was seen in two children and one had concomitant osteomyelitis. Group A beta-hemolytic streptococci were recovered from two patients with invasive bacterial infections. A total of 68 (38%) neurologic complications were observed. Cerebellar ataxia was present in 24, encephalitis was present in 17. Infectious complications occurred more frequently in younger children (median age: 2 years), whereas neurologic complications occurred at an older age (median age: 6 years). Hematologic complications were seen in nine children. There was a seasonal distribution of complications with a peak in January. CONCLUSION: Complications of varicella requiring hospitalization in immunocompetent children are more frequent than previously thought.     

Domestic violence: a tragedy behind the doors

OBJECTIVE: To explore the prevalence, type, frequency and causes of domestic marital violence among Turkish women in a socio-economically developed metropolitan setting. METHODS: A cross-sectional study was performed in 2003. All married women, aged 18 years and over, who were visiting any of the 50 primary health care units for different purposes were asked to participate in the study. Of 1427 asked, 1010 gave consent and completed face-to-face interviews. Multiple correspondence analysis, and logistic regression were used for statistical analyses. RESULTS: Domestic violence was statistically significantly associated with educational level. Illiterate women reported marital abuse 2.6 times more than university or more educated women. No statistically significant relationship was observed between domestic marital violence and women's age or occupation, marital duration or family income. The most frequently reported type of violence was physical, followed by psychological. Among women reporting domestic violence, those with the lowest educational level and income were experiencing all types of domestic violence frequently. CONCLUSION: Placing more importance on educating girls could be a key component of preventing domestic violence.     

Effects of N-acetylcysteine amide (NACA), a novel thiol antioxidant against glutamate-induced cytotoxicity in neuronal cell line PC12

Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions such as cerebral ischemia and Parkinson's disease. Elevated levels of glutamate are thought to be responsible for CNS disorders through various mechanisms causing oxidative stress induced by a nonreceptor-mediated oxidative pathway which blocks cystine uptake and results in depletion of intracellular glutathione (GSH). The newly designed amide form of N-acetylcysteine (NAC), N-acetylcysteine amide (NACA), was assessed for its ability to protect PC12 cells against oxidative toxicity induced by glutamate. NACA was shown to protect PC12 cells from glutamate (Glu) toxicity, as evaluated by LDH and MTS assays. NACA prevented glutamate-induced intracellular GSH loss. In addition, NACA restored GSH synthesis in a Glu (10 mM) plus buthionine-sulfoximine (BSO) (0.2 mM)-treated group, indicating that the intracellular GSH increase is independent of gamma-GSC (gamma-glutamylcysteinyl synthetase). The increase in levels of reactive oxygen species (ROS) induced by glutamate was significantly decreased by NACA. Measurement of malondialdehyde (MDA) showed that NACA reduced glutamate-induced elevations in levels of lipid peroxidation by-products. These results demonstrate that NACA can protect PC12 cells against glutamate cytotoxicity by inhibiting lipid peroxidation, and scavenging ROS, thus preserving intracellular GSH.