Platelet count, mean platelet volume and thrombocytopoietic indices in healthy women and men

Gender-dependent differences in platelet count have been demonstrated in few studies. In women platelet count is higher than in men, which seems to reflect different hormonal profiles or a compensatory mechanism associated with menstrual blood loss. The aim of the study was to assess platelet count, mean platelet volume and thrombocytopoietic indices in women and men. The study was conducted on healthy blood donors divided into groups: F - 60 women and M - 65 men. Platelet count and mean platelet volume were determined on a haematological analyser Advia 120, Bayer. The following thrombocytopoietic indices were measured: thrombopoietin concentration (ELISA), percentage of reticulated platelets (flow cytometry, COULTER EPICS XL) and absolute reticulated platelet count. RESULTS: Higher platelet count was noted in the group of women 252.35 +/- 41.25 x 10(9)/l as compared to men 221.87 +/- 37.63 x 10(9)/l (p = 0.0002). At the same time women had lower thrombopoietin concentration 156.50 +/- 57.18 pg/ml compared to men 180.46 +/- 60.98 pg/ml, (p = 0.03). No statistically significant differences were found in the mean platelet volume, percentage of reticulated platelets or absolute reticulated platelet count between group F and M. CONCLUSIONS: Platelet count is gender-dependent, being higher in women than in men. Thrombopoietin concentration is gender-dependent and is lower in women than in men. In physiological conditions, there is no correlation between platelet count and thrombopoietin concentration in women (r = -0.155) and men (r = -0.2586).     

Thymidylate synthase expression and p21WAF1/p53 phenotype of colon cancers identify patients who may benefit from 5-fluorouracil based therapy

Background

Studies on the expression of thymidylate synthase (TS) in colorectal cancers (CRCs) have failed to provide unequivocal prognostic or predictive information. Here, we assessed the prognostic significance of TS expression in Astler-Coller stage B2 and C CRCs defined by a p21^WAF1/p53 immunophenotype in patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy.

Methods

A cohort of 189 CRCs was asssessed for TS, p21^WAF1 and p53 expression on tissue microarrays using immunohistochemistry, and associations with disease-free survival (DFS) and overall survival (OS) of the patients were assessed using univariate and multivariate analyses.

Results

TS expression led to the stratification of patients with colon cancer, but not rectal cancer, with immunophenotypes other than p21^WAF1+/p53- (referred to as P&P) into subgroups characterized by a worse (P&P TS+) and a better (P&P TS-) DFS and OS, in univariate (P?=?0.006 and P?=?0.005, respectively) and multivariate (P?=?0.0004 and P?=?0.002, respectively) analyses. The p21^WAF1+/p53- immunophenotype was associated with a favorable prognosis, irrespective of TS expression.

Conclusions

The strong association observed between the P&P TS+ immunophenotype and a worse DFS and OS suggests a predictive significance of TS expression for 5FU-based adjuvant therapy in patients with colon cancers exhibiting the P&P immunophenotype. In addition, our findings suggest that the appropriate target for assessment of TS expression as a prognostic/predictive marker is a subgroup of colon cancers with an immunophenotype other than p21^WAF1+/p53-, and that only in this subgroup high TS expression is associated with an unfavorable DFS and OS. Therefore, we suggest that assessing TS expression in conjunction with p21^WAF1/p53 immunophenotyping of colon cancers may improve the selection of patients suitable for 5FU-based adjuvant chemotherapy.     

Chemical trapping of vancomycin: a potential strategy for preventing selection of vancomycin-resistant Enterococci

Emergence of antimicrobial resistance is among the most worrisome issues in public health worldwide. Vancomycin resistance is rapidly spreading, resulting in increased morbidity, mortality, and healthcare-associated costs. Multiple strategies are required to preserve the effectiveness of this essential antibiotic. It has been recently shown that biliary excretion of vancomycin following parenteral administration results in significant fecal concentrations of vancomycin that may lead to selection of vancomycin-resistant strains within the colon. In this study we present a novel strategy for preventing this undesired effect and its consequences, using chemical trapping of vancomycin by a tripeptide analog that mimics the natural bacterial vancomycin binding-site. Initially, we demonstrated that a tripeptide analog can neutralize vancomycin activity against Enterococci at a molar excess of 28. In the second phase, two chemical modifications, designed to attach the tripeptide to vancomycin covalently, were explored. Attachment of a 4-flurosulfonyl-benzoic acid (FSBA) moiety to the parent tripeptide resulted in vancomycin neutralization at a molar ratio of less than 4:1. Finally it was shown that the FSBA-bound tripeptide analog can prevent in-vitro selection of vancomycin-resistant Enterococci (VRE) from a mixed vancomycin susceptible/resistant population following exposure to vancomycin. These findings demonstrate the ability of the proposed strategy to prevent selection of VRE. The present proof-of-concept study provides the basis for further development of the proposed strategy. Further, this strategy may be implemented for combating resistance to other antimicrobials.     

Neurologic presentation, diagnostics, and therapeutic insights in a severe case of adenylosuccinate lyase deficiency

Epilepsy in adenylosuccinate lyase deficiency may be difficult to treat, and there is no standardized therapy. The authors describe a case of severe adenylosuccinate lyase deficiency resulting from a heterozygous mutation of the ADSL gene (p.D215H/p.I351T). The patient presented with tonic-clonic seizures, opisthotonus, tremor, and myoclonus in the 4th day of life. The seizures were refractory on various combinations of antiepileptic treatment. A ketogenic diet was introduced at the age of 2 resulting in a seizure-free period. The patient, however, developed a metabolic hyperchloremic acidosis with Fanconi syndrome, which disappeared a month after cessation of the diet at the age of 5. Since the withdrawal of the ketogenic diet, seizures have returned to a frequency of several times a day. In conclusion, a ketogenic diet could be considered a valid therapeutic option in patients with intractable seizures in a course of adenylosuccinate lyase deficiency; however, it requires a formal study.     

Behaviour change techniques applied in interventions to enhance physical activity adherence in patients with chronic musculoskeletal conditions: A systematic review and meta-analysis

Objective

To identify Behaviour Change Techniques (BCTs) applied in interventions to enhance physical activity (PA) adherence in patients with chronic musculoskeletal conditions and to investigate the effectiveness of these interventions in increasing PA adherence.

Zakażenia narządów płciowych u dziewcząt – profilaktyka i leczenie

Genital infections are a frequent diagnosis in pediatric and adolescent gynecology out-patient clinics, 2/5 of which relate to girls aged 0–14 years. The course of disease ranging from symptoms and ending on the treatment depends on many factors, foremost of the infection pathogen, but also on the child's age, coexisting diseases and sexual activity. Genital infections in girls can be caused by bacteria, viruses, fungi, parasites or factors of non-communicable. The most common symptoms of vulvovaginitis in girls are vaginal discharges with different color, texture and smell, occurring in 60–90% of the cases. Diagnosis of genital infections should begin with an anamnesis. During gynecological examination of external sexual organs, the vestibule of the vagina, urethra and area around the anus should be revealed for the presence of skin lesions and absences of the defects of interior genital. In sexually active girls cervix and vaginal walls should be also revealed. Personal hygiene and supportive treatment (sitz baths, vaginal irrigation, topical soothing agents, corticosteroids, antihistamines, loose cotton underwear, preparations of lactic acid) play a huge role in the prevention of vulvovaginitis in girls. Treatment of infections should be based on the result of bacteriological testing and antibiogram, in dose adjusted to age and body weight of girl.     

Hepatic and extrahepatic expression of glutathione S-transferase isozymes in mice and its modulation by naturally occurring phenolic acids

A simple plant phenolic acid, protocatechuic acid and a polyphenol, tannic acid are potential chemopreventive agents which inhibited the chemically induced carcinogenesis in many experimental models. We previously demonstrated that those compounds modulate the activity of xenobiotic detoxifying enzymes, including GST in mouse liver, kidney and epidermis. Intraperitoneal (i.p.) treatment with protocatechuic acid in the dose of 80mg/kg for three consecutive days increased the GST activity in liver and kidney. In case of tannic acid the same effect was observed in kidney after i.p. administration of the single dose of 80mg/kg. Topical application of phenolic acids resulted in enhancement of epidermal GST activity. The focus of this study was to further investigate the effects of these phenolic acids on the protein levels of GST isozymes in the same tissues using the treatment protocols used in our previous studies. The results confirmed the expression of GST alfa, mu, pi and theta in mouse liver, kidney and epidermis. Treatment with protocatechuic acid resulted in an increase of the expression of GST class mu in liver, but did not affect this isoform in skin and kidney. This compound inhibited the level of kidney GST pi by 35%. Tannic acid decreased the expression of GST mu, alpha and theta in liver. Application of the equimolar doses of both phenolic acids on mouse skin resulted in reduced level of the GST alpha protein. The results of our study indicate that, although moderate, the effect of protocatechuic acid and tannic acid on GST subunits in mice may play certain role in biological activity of these compounds. Of special importance could be the increased expression of GST mu in liver which is involved in detoxification of many carcinogens including polycyclic aromatic hydrocarbons.     

Novel 1,4-benzothiazine derivatives as large conductance Ca2+-activated potassium channel openers

The design and synthesis of a novel class of 1,4-benzothiazines targeted for the large-conductance calcium-activated potassium channels (BK) are presented. In vitro functional characterization of BK channel opening activity was assessed by measuring the relaxation of isolated rat aortic rings precontracted with KCl 20 mM. The results of this study show that the 1,4-benzothiazine heterocyclic nucleus is a suitable backbone for designing novel BK-openers; indeed, some of these new 1,4-benzothiazine derivatives had a vasorelaxant potency comparable or superior to that of reference BK-activator NS-1619 (1).     

Structure-activity relationship study on anti-HIV 6-desfluoroquinolones

On the basis of our recent findings that 6-aminoquinolones inhibit the HIV Tat-mediated transactivation, we have designed a broad series of derivatives identifying novel potent agents such as the 6-desfluoroquinolones 24 (HM12) and 27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, and latently HIV-1 infected cell cultures. We demonstrate here that highly potent molecules can be obtained by optimizing the substituent in the various positions of the quinolone nucleus.