Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core.

The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a core of noncrystalline and/or crystalline lipid, and a developed or developing collagenous cap. Total intimal volumes of the lipid-containing lesions, termed "fibrolipid lesions," ranged from 3 to 43 microliters, with the majority less than 16 microliters. Core lipid in the smallest lesions was located in the musculoelastic layer of the intima. In larger lesions the core extended luminally into the elastic hyperplastic layer, and cholesterol crystals were found more frequently. Total cholesterol concentration in fibrolipid lesions was similar to that in fatty streaks; however, the ratio of unesterified to total cholesterol was relatively high, similar to that found in fibrous plaques. It is concluded that 1) the formation of a lipid-rich core and cholesterol crystallization are early events in the development of many raised lesions; 2) the consistent association between the superficial layer of foam cells and the deep-lying lipid-rich core raises the possibility of an influence, possibly indirect, of foam-cell lipid metabolism on core formation; and 3) the fibrolipid lesion may represent one stage in a potential transitional morphologic sequence between fatty streak and fibrous plaque.     

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

1. 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.
2. PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K_i of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the K_i.
3. Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg⁻¹, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated K_i (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.
4. The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.
5. PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg⁻¹ (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.
6. Results of these studies are consistent with a role for 15-LO in atherogenesis.

     

Seroprevalence and geographic distribution of Dirofilaria immitis and tick-borne infections (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, and Ehrlichia canis) in dogs from Romania

Tick-borne diseases are of great concern worldwide. Despite this, in Romania there is only limited information regarding the prevalence of vector-borne pathogens in dogs. In all, 1146 serum samples were tested by SNAP(?) 4Dx(?) (IDEXX Laboratories, Inc., Westbrook, ME) for Anaplasma phagocytophilum, Borrelia burgdorferi, and Ehrlichia canis antibodies, and for Dirofilaria immitis antigen. The correlation between positive cases and their geographic distribution, as well as potential risk factors (age, sex, breed, type of dog, habitat, and prophylactic treatments) were evaluated. Overall, 129 dogs (11.3%) were serologically-positive to one or more of the tested pathogens. The seroprevalence for the four infectious agents were: A. phagocytophilum 5.5% (63/1146), D. immitis 3.3% (38/1146), E. canis 2.1% (24/1146), and B. burgdorferi 0.5% (6/1146). Co-infection with E. canis and A. phagocytophilum was registered in 2 dogs (0.2%). The geographical distribution of the seropositive cases suggests clustered foci in southern regions and in the western part of the country for D. immitis, and in the southeastern region (Constan?a County) for E. canis. A. phagocytophilum and B. burgdorferi showed a homogenous distribution, with a tendency for Lyme-positive samples to concentrate in central Romania. For D. immitis, A. phagocytophilum, and E. canis, administering prophylactic treatments was a risk factor associated with infection. Another associated risk factor was the type of dog (stray dogs were at risk being positive for D. immitis, shelter dogs for E. canis, and hunting dogs for B. burgdorferi). The prevalence of D. immitis was significantly higher in males and in dogs older than 2 years. This survey represents the first data detailing A. phagocytophilum and E. canis seroprevalence in Romanian dogs, and the most comprehensive epidemiological study on vector-borne infections in dogs from this country.     

Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions G^E for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.     

A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres

Journal of Neurology - To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family. The patients were recruited from our clinic. Muscle biopsy and whole-exome...     

La pensée et le langage par le corps dans la schizophrénie

Connections between body and psyche are regularly studied in the field of psychosis. One of the reasons of that recurrence is the fact that schizophrenic psychosis deconstructs the discursive system and exposes its bodily roots. In the first part of this paper, we remind several authors (Dolto, Pankow, Aulagnier, Golse, Delion, Piaget, Stern i.e.), whose works are showing how the mind develops on the basis of sense - and bodily experiences. In the second part, we examine the specificity of the schizophrenia as regression to the autoerotism and we mention Freud's idea of the “organ's language”. The organ's language represents the use of bodily symbols into the discourse; those symbols have to be interpreted like dreams. Finally, two clinical examples illustrate those elements. We examine the idea that, even if the nosographic category “schizophrenia” has not necessarily to be defended, there is perhaps a common clinical feature defined by the place of the body in the discourse.     

Specifics of food intake by schoolchildren in the rural areas of Moldova

149 schoolchildren, 14-15 years old, from 4 rural communities pending on 4 different Moldova counties have been investigated using the one day questionnaire technique. From the entire studied group, only 7.4% are do not eat breakfast before attending school. 35.5% of the schoolchildren consider their sugar intake to be excessive, without taking into account the sugar major role in nervous cell function. The average daily intake for fresh fruits, vegetables and milk is in most cases adequate, but significant differences are present between the communities, related with the socio-economic status of the families and, also, with nutritional.     

Headache in children and adolescent in ambulatory practice

Headache in children and adolescent represents one of the most frequent and potentially severe pathological conditions, requiring a paediatric consult. The purpose of the study was to establish the headache prevalence from the total paediatric consultations in ambulatory practice as well as to establish the main etiological causes of the headache. The study, including 400 children and adolescents (M/F ratio=150/250, U/R ratio=290/110) with headache selected from 3100 cases between 2003 and 2004, in two practices (one general paediatric office and one paediatric neuropsychiatry office) from the Outpatient Clinic of the "Sf. Spiridon" Hospital of Iasi, has shown a prevalence of headache of 12.9%, the most affected age group being that of 5-12 years (52.5%). The etiologic study proved a high frequency of trauma 46.25%, ophthalmologic diseases 13.28%, psychogenic headache 10.75%, migraine 10%, general causes (infections, anaemia, hypoglycaemia) 9%, ENT causes 6.25%, intracranial causes 0.75%. The study confirms the necessity of a multidisciplinary approach, most causes being benign and the prognosis favourable in most cases.     

Innovation and Translation Efforts in Wireless Medical Connectivity, Telemedicine and eMedicine: A Story from the RFID Center of Excellence at the University of Pittsburgh

Translational research has recently been rediscovered as one of the basic tenants of engineering. Although many people have numerous ideas of how to accomplish this successfully, the fundamental method is to provide an innovative and creative environment. The University of Pittsburgh has been accomplishing this goal though a variety of methodologies. The contents of this paper are exemplary of what can be achieved though the interaction of students, staff, faculty and, in one example, high school teachers. While the projects completed within the groups involved in this paper have spanned other areas, the focus of this paper is on the biomedical devices, that is, towards improving and maintaining health in a variety of areas. The spirit of the translational research is discovery, invention, intellectual property protection, and the creation of value through the spinning off of companies while providing better health care and creating jobs. All but one of these projects involve wireless radio frequency (RF) energy for delivery. The remaining device can be wirelessly connected for data collection.