Platelet-derived growth factor and its receptor in blood cell differentiation and neoplasia

Platelet-derived growth factor (PDGF) is a family of dimeric protein molecules synthesized by differentiated, non-dividing and proliferating blood cells. Experimental findings indicate that PDGF is involved in development and/or maintenance of physiological functions of certain normal blood cells. Also, PDGF synthesis correlates with certain blood cell proliferative diseases caused either spontaneously or associated with viral infection. There is increasing evidence that the diverse effects of PDGF in both normal and abnormal physiological functions of blood cells may be regulated at the level of its receptor. New experimental findings are discussed relating to PDGF receptors in normal leukemic, and virally-infected human cells of myeloid and lymphocytic lineages. At specific developmental stages this regulation may take the form of PDGF and its receptor being expressed or co-expressed; the unmodified or modified form of receptor that specifically interacts with PDGF; the cellular site at which the PDGF-receptor interacts with its ligand; and co-expression of the PDGF-receptor with other receptors associated with specific cell lineage or functions. Elucidation of events involved in synthesis, processing, and interactions of PDGF isoforms and their respective receptors will enable us to develop pharmacological means that may either interfere with, or enhance these desired blood cell functions. This review focuses on PDGF and its receptor in human blood cell differentiation and neoplasia.     

Recurrent renal cell carcinoma arising in Wilms' tumor.

A 19-month-old black girl had a radical nephrectomy for a Wilms' tumor that contained areas of epithelium indistinguishable from renal cell carcinoma. She was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence. The recurrent tumor was histologically renal cell carcinoma with no identifiable Wilms' tumor elements. The child died with recurrent and metastatic tumor 13 months after nephrectomy. Pathologic, immunoperoxidase, and flow cytometric studies of this unusual case are presented.     

Chios Mastic Gum: A Plant-produced Resin Exhibiting Numerous Diverse Pharmaceutical and Biomedical Properties

Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var. chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO consist of nearly 70 constituents and have demonstrated numerous and diverse biomedical and pharmacological properties including (a) eradication of bacteria and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the mouth and saliva; (b) amelioration or dramatic reduction of symptoms of autoimmune diseases by inhibiting production of pro-inflammatory substances by activated macrophages, production of cytokines by peripheral blood mononuclear cells in patients with active Crohn's disease, and suppression of production of inflammatory cytokines and chemokines in an asthma model in mice; (c) protection of the cardiovascular system by effectively lowering the levels of total serum cholesterol, low-density lipoprotein and triglycerides in rats, and protection of low-density lipoprotein from oxidation in humans; (d) induction of apoptosis in human cancer cells in vitro and extensive inhibition of growth of human tumors xenografted in immunodeficient mice; and (e) improvement of symptoms in patients with functional dyspepsia. Collectively taken, these numerous and diverse medical and pharmaceutical properties of CMG and MGO warrant further research in an effort to enhance specific properties and identify specific constituent(s) that might be associated with each property.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

In-111-labeled white blood cell uptake in noninfected closed fracture in humans: prospective study

Since indium-111 white blood cell (In-111 WBC) scintigraphy is often used to evaluate for osteomyelitis in bone fractures, it is important to know if noninfected fractures have In-111 WBC uptake. Twenty-seven noninfected closed fracture sites in 19 patients were prospectively evaluated with technetium-99m methylene diphosphonate bone scintigraphy and In-111 WBC scintigraphy. In-111 WBC uptake was present in 41% of the 27 sites. In the 11 positive sites, the In-111 WBC uptake was 1+ (definite but minimal) in 55%, 2+ (moderate) in 36%, and 3+ (marked) in 9%. The visual intensity of the radioactive uptake on In-111 WBC scintigrams relative to that on bone scintigrams was less in 82%, equal in 9%, and greater in 9%. The visual size of the area of uptake on In-111 WBC scintigrams and bone scintigrams was smaller in 36%, equal in 55%, and greater in 9%. Factors that may help distinction of In-111 WBC uptake due to fracture alone from infection associated with fracture are discussed.     

Alcohol exposure during the brain growth spurt promotes hippocampal seizures, rapid kindling, and spreading depression

BACKGROUND: Epilepsy is a prominent sign of brain dysfunction and a cause of substantial disability in some children with fetal alcohol syndrome. The hippocampal formation is vulnerable to alcohol-induced pathologic changes and is the source of seizure activity in a variety of epileptic conditions. This study tests the hypothesis that developmental alcohol exposure facilitates epileptic activity and promotes kindling within hippocampal circuitry. METHODS: Rat pups received either a moderate dose (2.0 g/kg) or a high dose (3.75 g/kg) of alcohol via intragastric intubation over postnatal days 4 to 10. Intubated control and suckle control groups were also included. Upon reaching adulthood (postnatal days 85-100), the rats underwent electrophysiologic testing. A double-barrel potassium-sensitive microelectrode was placed into the right dentate gyrus stratum granulosum for the recording of extracellular field potential and extracellular potassium concentration. Stimuli were delivered via an electrode positioned in the CA3 subregion of the left hippocampus. To assess whether alcohol promotes hippocampal seizures and rapid kindling, the parameters of maximal dentate activation (MDA) were measured before, during, and after a series of stimulation-induced seizures. RESULTS: Developmental exposure to the high dose of alcohol permanently altered several parameters of MDA. Time to onset of MDA and stimulus threshold for afterdischarge production were both decreased, whereas the duration of the afterdischarge was increased. Although the moderate alcohol dose reduced time to onset of MDA, it did not affect any other MDA parameters. Over the course of the repeated induced seizures, spreading depression occurred more often and with fewer stimuli in the high-dose alcohol group than in any other group. The series of repeated electrographic seizures induced rapid kindling in all of the treatment groups. However, the kindling effect was enhanced in a dose-response manner by the previous alcohol exposures. CONCLUSIONS: These findings demonstrate that exposure to alcohol during brain development can permanently alter the physiology of the hippocampal formation, thus promoting epileptic activity, enhancing kindling, and facilitating spreading depression. The relative roles of alcohol intoxication and withdrawal in these abnormal physiologic responses remain unknown.     

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients： The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance

OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI.