Volume 2, Issue 4

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.

The knowledge of grape and wine is as old as the cultural history of mankind. Moderate consumption of wine can be beneficial in healthy individuals. It is also known from ancient times that it can cause acute and chronic damage when consumed in great quantities. The disinfectant effect of its use in ointments has been observed already in the antiquity. Polyphenols, among them resveratrol, have generated a great amount of scientific research due to their in vivo and in vitro antioxidant capabilities. For decades, red wine was thought to have beneficial effects on cardiovascular health. This relation was clearly established in the French Paradox phenomenon as well as in the Mediterranean diet. The French Paradox is defined as a low incidence of coronary heart disease, while consuming a diet rich in saturated fat. The cause of this phenomenon is the usually wine drinking in small quantity, supposingly in the consequence of polypenols in red wine. The use of ointments containing polyphenols of wine and the cosmetic treatments with them can be advantageous in the treatment and prevention of some diseases of the skin and the joints, due to its free radical scavenging effect. In healthy individuals the consumption of a moderate amount of 1 to 2 dl wine a day may reduce the mortality of cardiovascular diseases. However, also this quantity can be associated with detrimental effects in pregnant women, in children and in patients with various organic, particularly hepatic, diseases as well as in case of regular administration of certain medicines.

Navigation has become widely integrated into regular endoprosthetic procedures, but clinical use of navigation systems in orthopaedic trauma has only been implemented in a few indications. Navigation systems enable an accuracy of 1 mm or 1 degree. Navigation can achieve higher precision when it is combined with different imaging modalities, including preoperative computer tomography (CT), intraoperative CT, two-dimensional fluoroscopy, and, recently, intraoperative three-dimensional fluoroscopy. The precision of the navigation system can be influenced by the surgeon as well as by the camera system, type of reference marker, and the registration process. Recent developments in orthopedic trauma navigation allow for bilateral femoral anteversion measurements, noninvasive registration of an uninjured thigh, and intraoperative three-dimensional fluoroscopy-based pedicle screw placement. Although the use of navigation has provided initial positive results in trauma care, prospective clinical studies remain to be performed.

We studied the course of infection with human immunodeficiency virus type 1 (HIV-1) in relation to apolipoprotein E (APOE) polymorphism found for 209 Italians treated at Infectious Disease Clinics in Rome and Modena. Clinically, patients were classified into four groups according to the yearly rate of decline in CD4+ cell count (LTNP: long-term non-progression; SLOW, ’NORMAL’ or RAPID). Patients at both extremes of the clinical spectrum, i.e. those who rapidly progressed to AIDS and those with stable high CD4 cell counts, had few APOE ɛ4 and ɛ2 alleles (P = 0.04). Detailed clinical information was then used to construct four model-based clinical profiles using grade-of-membership analysis (GoM), predictive of APOE genotypic frequencies: 1. The clinical profile associated with good long-term prognosis lacked ɛ2 (P=0.01); 2. Disease progression to AIDS was associated with ɛ4 and ɛ2, most evident for zidovudine-lamivudine regimens without a protease inhibitor (P = 0.03); and, 3. AIDS patients had low ɛ4 and ɛ2 frequencies, consistent with a high mortality rate among ɛ4+ and ɛ2+ AIDS patients. These findings suggest allele-specific immunomodulatory effects involving inherited APOE isoform important enough to alter the clinical course of HIV infection and, possibly, drug efficacy. They imply a connection between lipid metabolism and immunity potentially relevant to common disorders.

Short fragments of typical or atypical opioid peptides, lacking the whole four amino acid sequence of the enkephalin motif, can preserve a significant percentage of the analgesic activity of the original peptides. This paper investigates the importance of the amino-acidic sequence of minimum structure typical opioid peptides for the analgesic activity. Different groups of rats were treated with 1) Gly-Tyr, 0.5 mg/rat i.t., 2) Tyr-Gly, 0.5 mg/rat i.t., 3) Tyr-Gly-Gly, 0.5 mg/rat i.t., 4) Gly-Gly-Phe-Leu, 0.5 mg/rat i.t., 5) Leu-enkephalin, 0.5 mg/rat i.t.. The analgesic effect of the tested substances was appreciated through the nociceptive threshold for thermal (plantar test) and mechanical nociception (algesimetric test). Fragments of typical opioid peptides elicited antinociceptive activity only when a tyrosine residue was present at the N-terminal end of the amino-acidic sequence. The presence of Nterminal tyrosine provides affinity for the opioid receptors and significant analgesic activity. The intensity of the antinociceptive effect was directly proportional with the length of the amino-acidic sequence. The inhibition of the analgesic effect by previous administration of naloxone proves that this effect is mediated through the opioid system.

Cholinesterase inhibitors are currently used in the therapy of different kind of dementia to improve brain memory functions. The acetylcholinesterase inhibitor metrifonate was studied in naive rats and in rats with a model of sodium nitrite-induced hypoxia. One active avoidance test and in two passive avoidance tests were used. In the active avoidance test metrifonate increased the number of avoidances during the learning session only. In both passive avoidance tests, metrifonate prolonged latency differently during the learning session and in short-term or in long-term memory retention. Hypoxic rats showed lower numbers of avoidances in learning and memory retention sessions. Metrifonate increased the number of avoidances during the learning session for hypoxic rats. In the step-through passive avoidance test, metrifonate increased the latency of reactions in the learning session and in long-term memory retention tests. In the step-down passive avoidance test, the groups with hypoxia and metrifonate did not change the latency of reaction in the learning and long-term memory retention sessions, but increased the latency of reactions in the short-term memory retention test. Morphological data showed a significant impaired neuronal structure in a CA1 zone of the hippocampus in hypoxic rats and a tendency to preserving in rats treated with metrifonate. Our results suggest that metrifonate improves cognitive functions in naive and in hypoxic rats.

In the current study, we examined the effects of Cd on Cd, Cu, Zn and Fe levels in placenta and maternal and fetal plasma and tissues, the placental weight, total fetal and maternal body weights, and fetal and maternal tissue weights during pregnancy. A total of 21 adult female rats were treated during gestation with drinking water containing one of the following: 70 mg/L of CdCl2, a combination of 70 mg/L of CdCl2 and 70 mg/L of CuSO4, or no addition (control). Placenta Cu and Fe levels, fetal liver and kidney Cu levels, and fetal liver tissue weights were lower in the group administered Cd than in the control group. Also, Cd levels in the placenta, maternal and fetal liver, and maternal kidney were higher in the group treated with Cd than in controls. In the group administered both Cd and Cu, fetal body and tissue weights did not change, but Cd levels in the placenta, maternal and fetal liver, and maternal kidneys were higher than in controls. Zn and Fe levels in the maternal kidney and fetal liver were also lower in this group. Cd exposure during pregnancy resulted in Cd accumulation in maternal and fetal tissues during pregnancy and a decrease in the total weight of fetuses, and the combination of Cd and Cu caused some changes in the both maternal and fetal levels of Cu, Zn, and Fe, but it did not cause changes in the total fetal body weight or the weights of individual tissues.

To evaluate the association of The study is to evaluate the association of metabolic syndrome (MS) and its components on brachial-ankle pulse wave velocity (baPWV), an indirect marker of subclinical atherosclerosis, in middle-aged Taiwanese males. A total of 442 men aged 40 to 65 years were included in this cross-sectional survey. Arterial stiffness was measured using a non-invasive method by baPWV. MS is defined by the presence of ≥ 3 components using the modified National Cholesterol Education Program criteria. The mean baPWV was 1478.6 and 1520.3 cm/sec in normal-weight and overweight adults, respectively. Age, systolic blood pressure (BP), diastolic BP, and fasting blood glucose (FBG) correlated with baPWV levels in normal-weight and overweight males. In multiple logistic regression analysis, after adjusting for potential confounders, MS and its components (such as high BP and high FBG) were significantly associated with abnormal baPWV (≥1400 cm/sec) (p < 0.001). MS and its components are significantly associated with abnormal baPWV in Taiwanese middle-aged males and in addition, high BP was the component of MS most significantly associated with abnormal baPWV.

This study was designed to compare perioperative blood pressure (BP) management in hypertensive patients with phaeochromocytoma undergoing preoperative α-blockade and in patients with other suprarenal gland tumors. Perioperative hemodynamic data and immediate postoperative outcome in two groups undergoing adrenalectomy were compared. 483 medical charts from urologic patients with tumors were analyzed. In the hypertensive (n = 168) group, 20 patients with suprarenal gland tumors were identified (phaeochromocytoma n = 11, other tumors n = 9). Demographic data, intraoperative consumption of fentanyl and phentolamine, preoperative hospital stay and postoperative ICU stay were compared. Mean arterial pressure (MAP) was registered on the day before surgery, before anesthetic induction, during surgery, and upon admission in the intensive care unit (ICU). Although BP values did not differ significantly on the day before anesthesia, before induction and during operation, significantly more antihypertensive drugs were used for BP regulation in phaeochromocytoma patients versus the other tumor group. The phaeochromocytoma group required significantly more fentanyl during surgery (370±87 vs. 242±35 µg; p = 0.04). MAP upon ICU admission was significantly lower (85.1 vs. 97.4, p = 0.02) after adrenalectomy in phaeochromocytoma patients versus the other tumor group. The postoperative MAP decreased significantly in the phaeochromocytoma group (21.51 mmHg, p = 0.005), whereas significant differences according to preoperative values were not observed in the other tumor group (5.5 mmHg, p = 0.416). Prolonged preoperative hospital stay (24.6 vs. 10.0 days, p = 0.005) and ICU stay were registered in the phaeochromocytoma group. Pheochromocytoma patients had more pronounced perioperative BP oscillations, needed more antihypertensive drugs, analgesics and required prolonged hospital stay than patients with other adrenal tumors. Prolonged α-blockade may have contributed to these effects.

We examined the association between overweight/gender and skipping breakfast among adolescent students in Tehran city using a cross-sectional study and a multistage random sampling method. All educational zones in Tehran city were covered during the educational year of 2000–01. In total, 2321 students aged 11–16 years (1068 male; 1263 female) participated in the study. Weight and height were measured and body mass index (BMI; kg/m2) was calculated. Overweight, pre-obesity and obesity were defined as BMI ≥ 85th, 85th to 95th, and ≥ 95th percentile of age-sex-specific BMI reference values, respectively. Self-reported frequency of breakfast consumption was categorized as usual/always, often, and rarely/never (5–7, 2–4 and 0–1 times/wk, respectively). Student’s t and Chi-square tests were employed to analyze the data. Statistical inferences were made at α = 0.05. In boys and girls, the mean ± standard deviation of BMI was 19.8 ± 4.0 and 20.6 ± 4.1 kg/m2, the 18.8% and 23.1% were overweight, and 7.3% and 8.3% were obese, respectively. There was a significant difference in the frequency of breakfast consumption between obese and normal male students (P < 0.001). Differences between pre-obese and normal, and obese and normal female students were also significant (P < 0.002 and P < 0.001, respectively). A significant difference was found in the frequency of breakfast consumption between male and female adolescents in all three categories (P < 0.001). These results suggest that obese and female adolescents are more likely to skip breakfast than their normal and male peers and are therefore at higher risk for growth deficits and low educational performance. Preventive/educational programs are urgently needed in this age group.

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for diffuse large B-cell lymphoma (DLBCL) patients; however, the therapeutic efficacy seems unsatisfactory. Additional rituximab will improve the cure rate, but it is not popular in China because of its increased medical cost. Germinal center B-cell (GCB) and non-GCB subtypes distinction have been described as independent prognostic factors, and provides likelihood for cure with chemotherapy. The aim of the study is to explore the association between Immunophenotype and treatment regimen. Between August 2003 and May 2006, 66 patients with DLBCL were enrolled, according to immunohistochemistry results (GCB and non-GCB phenotype), randomly assigned to receive either six to eight cycles of CHOP every 2 weeks or standard CHOP every 3 weeks. After a median follow-up duration of 32 months (range of 4 to 42 months), an estimated 3-year overall survival (OS) rate for the GCB patients were 68.2% and 55.6% for the biweekly CHOP regimen and standard CHOP regimen respectively, while the data were 62.8% and 37.9% respectively for the non-GCB cases. The biweekly CHOP therapy showed higher efficacy than standard treatment, and its superiority was more obvious with the non-GCB subgroup. All rights reserved.

Bone scintigraphy, although quite sensitive to detect skeletal lesions, has a comparatively low specificity. Hybrid-cameras combining single-photon emission computed tomography (SPECT) and spiral-CT offer the opportunity to correlate scintigraphic information with high-quality visualization of morphology in one session. This may lead to an improvement in diagnostic accuracy and anatomic lesion localization. We present 11 patients, who underwent SPECT/CT of the feet (n=10) and hands (n = 1). The examinations were performed due to pain in foot or hand with the following suspected clinical diagnoses: arthrosis (n=1); fracture (n=3); osteomyelitis (n=4); reflex dystrophia (n=1); and, pain of unclear origin (n=2). All patients underwent SPECT/CT hybrid imaging using a dual-headed SPECT camera integrated with a 2-slice spiral CT scanner in one gantry. SPECT, CT, and SPECT/CT were evaluated independently from each other with respect to main diagnosis, anatomic lesion localization, and detection of a possible additional diagnosis. SPECT/CT improved lesion localization in 8 of 11 patients (73%) in comparison to SPECT alone, and in 4 of 11 patients (36%) in comparison to CT alone. Diagnostic accuracy was improved in 4 of 11 patients (36%) in comparison to either SPECT or CT alone. In conclusion, skeletal SPECT/CT improves diagnostic accuracy and lesion localization of orthopedic disorders in the feet and hands. The obtained results encouraged extensive studies to further investigate the potential gain in diagnostic accuracy brought about by SPECT/spiral-CT hybrid imaging in orthopedic disorders of the peripheral extremities.

Amelogenesis imperfecta (AI) is an inherited tooth disorder with widely varying phenotypes. The aim of this study was to determine the microhardness and microstructure characteristics of the enamel in AI teeth. The AI phenotypes examined were hypoplastic (pitted and smooth form), hypomaturated, and hypocalcified. Six AI patients were diagnosed according to clinical characteristics. The microhardness of the enamel was measured on axial cuts of AI teeth acquired from the patients. The measurements were done on several sites from the enamel surface towards the dentine-enamel junction using the Vickers scale. Values of microhardness were compared to corresponding control teeth. The microstructure of AI enamel types was evaluated using scanning electron microscopy. The values of microhardness in pitted hypoplastic AI samples were, on average, lower compared to the control enamel and dropped markedly towards the dentine-enamel junction. The smooth hypoplastic enamel was not only extremely thin but also much softer than control enamel. The values for hypomaturated AI fluctuated, but the palatal sites were markedly softer than in the control tooth. Hypocalcified enamel was the softest, with values resembling those of dentin. Microstructural changes varied from altered orientation of enamel prisms in pitted hypoplastic AI to lack of normal prismatic structure and severe porosity in hypocalcified AI. The present results suggest different microhardness profiles and microstructures in each phenotype. Variations among phenotypes are expected with larger case selection in this genetically heterogeneous disease.

Poland, like other countries with previously dominant state healthcare systems, has introduced ownership transformation in the healthcare structure. These changes, however, are being accomplished without a clearly defined state policy in this area. The aim of the present study was to assess the course and effects of ownership transformation in outpatient healthcare and hospitals. Data were collected from publications of the Central Statistical Office, which provided information on the numbers of outpatient healthcare institutions, medical practices, general hospitals, and services they provided. The healthcare ownership transformation has divided the medical services market into public and nonpublic providers. In addition, privatization of outpatient healthcare facilities precedes privatization of hospitals, outpatient institutions providing primary healthcare were privatized first; the subsequent stage included those providing specialized services, at first privatization of ambulatory medical infrastructure preceded privatization of services in urban areas, whereas in rural areas, privatization of services preceded structural privatization, privatization provides favorable conditions to improve territorial availability of outpatient healthcare in urban areas, medical practices, although numerous, are of little importance in providing services, the hospital ownership transformation is at its initial stage, and structural ownership transformation in the Polish healthcare system is subject to market rules.

Hemocholecyst is a rare disorder that has been reported in patients with gallstones. Previous reports describe cholecystitis resulting from hemocholecyst after iatrogenic trauma. We report the first case of acute cholecystitis secondary to hemocholecyst in a patient with Hemophilia A.