Platelet microparticles: Detection and assessment of their paradoxical functional roles in disease and regenerative medicine

There is increasing research on and clinical interest in the physiological role played by platelet microparticles (PMPs). PMPs are 0.1–1-μm fragments shed from plasma membranes of platelets that are undergoing activation, stress, or apoptosis. They have a phospholipid-based structure and express functional receptors from platelet membranes. As they are the most abundant microparticles in the blood and they express the procoagulant phosphatidylserine, PMPs likely complement, if not amplify, the functions of platelets in hemostasis, thrombosis, cancer, and inflammation, but also act as promoters of tissue regeneration. Their size and structure make them instrumental in platelet–cell communications as a delivery tool of platelet-borne bioactive molecules including growth factors, other signaling molecules and micro (mi)RNA. PMPs can therefore be a pathophysiological threat or benefit to the cellular environment when interacting with the blood vasculature. There is also increasing evidence that PMP generation is triggered during blood collection, separation into components, and storage, a phenomenon potentially leading to thrombotic and inflammatory side effects in transfused patients. Evaluating PMPs requires strict pre-analytical and analytical procedures to avoid artifactual generation and ensure accurate assessment of the number, size repartitioning, and functional properties. This review describes the physical and functional methods developed for analyzing and quantifying PMPs. It then presents the functional roles of PMPs as markers or triggers of diseases like thrombosis, atherosclerosis, and cancer, and discusses the possible detrimental immunological impact of their generation in blood components. Finally we review the potential function of PMPs in tissue regeneration and the prospects for their use in therapeutic strategies for human health.     

Self-regulation of smoking intensity. Smoke yields of the low-nicotine, low-'tar'cigarettes

It has been assumed for some time that the ‘tar’and nicotine data for individual cigarette brands, as reportedby the Federal Trade Commission (FTC), do not adequately reflectthe levels of exposure to toxic and carcinogenic agents in thesmoke. The trend of decreasing ‘tar’ and nicotineyields of the sales-weighted average US cigarettes was not followedby a proportionate decline of lung cancer incidence and mortalityrates. Utilizing a ‘tobacco smoke inhalation testing system’,we determined smoking profiles for four men and four women whosmoked low-nicotine cigarettes (     

Inhibitory effect of probucol on benzo[a]pyrene induced lung tumorigenesis

The effects of probucol, a clinically used cholesterol loweringand antioxidant drug, on benzo[a]pyrene (B[a]P) induced pulmonaryand forestomach tumorigenesis as well as induction of colonicaberrant crypt foci (ACF) in female A/J mice was investigated.Diet containing 1% probucol fed prior to, during and after 8bi-weekly 1 mg/mouse oral intubations of B[a]P reduced the numberof pulmonary adenomas by 52% (P < 0.001) and the number offorestomach tumors by 31%nt. The 0.06% probucol diet also resultedin decreased tumor formation but the differences did not reachstatistical significance. Both probucol diets significantlyreduced the numbers of large ACF, putative preneoplastic lesionsof the colon mucosa, but showed no effects on the total numbersof ACF. The results of this study suggest that probucol mayalso be useful as a chemopreventive agent, in addition to beinga cholesterol lowering and anti-atherogenic drug with low toxicity.     

Attitudes to voluntary sterilization in Serbia: women's and gynecologists' points of view.

OBJECTIVES: The question if voluntary sterilization is accepted in Serbia has been imposed for research, regardless of the fact that this birth control method is neither accessible nor promoted. METHODS: The attitudes of women who decided to terminate pregnancy and of gynecologists from various parts of Serbia were explored by specially designed anonymous questionnaires. RESULTS: More than half of the surveyed women believe that voluntary sterilization should be available in Serbia and almost half would subject themselves to this surgical procedure. Younger women, respondents with secondary education, those who have the desired number of children, as well as those who have a good relationship with partner, who have experienced a large number of abortions, namely those who wish to use contraception, are more open to voluntary sterilization. The majority of gynecologists think that voluntary sterilization should become available in Serbia. Medical and eugenic reasons are, according to their opinion, the main indications for sterilization. The gynecologists lack current knowledge about this contraceptive method, and would not accept to use voluntary sterilization themselves. CONCLUSIONS: There is a need for voluntary sterilization as a contraceptive choice in Serbia. Relevant knowledge of women as well as gynecologists about voluntary sterilization should be improved.     

Widespread tinea corporis caused by Trichophyton rubrum with non-typical cultural characteristics – diagnosis via PCR

From the epidemiological point of view, Trichophyton rubrum is the most important dermatophyte in the Western world. Mostly, the lesions of fungal infections of the skin are restricted and circumscribed. Immunodeficiency, diabetes or treatment with steroids, however, favour widespread disease involving the entire integument. In the present study, we describe a patient without immunodeficiency or diabetes presenting with widespread tinea corporis caused by T. rubrum . The fungal isolate showed atypical morphological features. Moreover, the typical metabolic features (negative urease test, production of red pigment on potato dextrose agar) were expressed with delay after 6 weeks of cultivation. Thus, sequencing of the internal transcribed spacer of the ribosomal DNA was applied to identify the fungal isolate and led us to the correct diagnosis, before conventional mycological methods were successful.     

Neurorehabilitation of Upper Extremities in Humans with Sensory‐Motor Impairment

Today most clinical investigators agree that the common denominator for successful therapy in subjects after central nervous system (CNS) lesions is to induce concentrated, repetitive practice of the more affected limb as soon as possible after the onset of impairment. This paper reviews representative methods of neurorehabilitation such as constraining the less affected arm and using a robot to facilitate movement of the affected arm, and focuses on functional electrotherapy promoting the movement recovery. The functional electrical therapy (FET) encompasses three elements: 1) control of movements that are compromised because of the impairment, 2) enhanced exercise of paralyzed extremities, and 3) augmented activity of afferent neural pathway. Liberson et al. 1 first reported an important result of the FET; they applied a peroneal stimulator to enhance functionally essential ankle dorsiflexion during the swing phase of walking. Merletti et al. 2 described a similar electrotherapeutic effect for upper extremities; they applied a two‐channel electronic stimulator and surface electrodes to augment elbow extension and finger extension during different reach and grasp activities. Both electrotherapies resulted in immediate and carry‐over effects caused by systematic application of FET. In studies with subjects after a spinal cord lesion at the cervical level (chronic tetraplegia) 3 - 5 or stroke 6 , it was shown that FET improves grasping and reaching by using the following outcome measures: the Upper Extremity Function Test (UEFT), coordination between elbow and shoulder movement, and the Functional Independence Measure (FIM). Externally applied electrical stimuli provided a strong central sensory input which could be responsible for the changes in the organization of impaired sensory‐motor mechanisms. FET resulted in stronger muscles that were stimulated directly, as well as exercising other muscles. The ability to move paralyzed extremities also provided awareness (proprioception and visual feedback) of enhanced functional ability as being very beneficial for the recovery. FET contributed to the increased range of movement in the affected joints, increased speed of joint rotations, reduced spasticity, and improved functioning measured by the UEFT, the FIM and the Quadriplegia Index of Function (QIF).