HCG--A new kid on the block in prematurity prevention.

Human chorionic gonadotropin (HCG) is a molecule with multiple endocrine, paracrine, and immunoregulatory actions. Its importance for the enhancement of fertility, successful implantation, and survival of the conceptus in early gestation is recognized. However, studies conducted worldwide in recent years indicate that HCG may also play a significant role in maintaining pregnancy well after the first trimester. Emerging evidence suggests that different biomolecular and physiologic effects of HCG are concordantly directed toward inhibition of myometrial contractility to maintain pregnancy. These studies have prompted preliminary animal and human testing of HCG for the prevention of preterm birth. This article reviews the current knowledge as well as the future perspectives on HCG as a useful new tool in prematurity prevention.     

The aging brain, a key target for the future: The protein kinase C involvement

The brain represents the primary centre for the regulation and control of all our body activities, receiving and interpreting sensory impulses and transmitting information to the periphery. Most importantly, it is also the seat of consciousness, thought, emotion and especially memory, being in fact able to encode, store and recall any information. Memory is really what makes possible so many of our complex cognitive functions, including communication and learning, and surely without memory, life would lose all of its glamour and purpose. Age-associated mental impairment can range in severity from forgetfulness at the border with pathology to dementia, such as in Alzheimer's disease. In recent years, one of the most relevant observations of research on brain aging relates to data indicating that age-related cognitive decline is not only due to neuronal loss, as previously thought; instead, scientists now believe that age-associated functional changes have more to do with the dysfunctions occurring over time. Within this context a prominent role is certainly played by signal transduction cascades which guarantee neuronal cell to elaborate coordinated responses to the multiple signals coming from the outside and to adapt itself to the environmental changes and requests. This review will focus the attention on protein kinase C pathway, with a particular interest on its activation process, and on the role of protein-lipid and protein-protein interactions to selectively localize the cellular responses. Furthermore, information is emerging and will be discussed on the possibility of mRNA stabilization through PKC activation. This review will also approach the issue on how alterations of these molecular cascades may have implications in physiological and pathological brain aging, such as Alzheimer's disease.     

ReProComet: a new in vitro method to assess DNA damage in mammalian sperm.

The increasing request of chemical safety assessment demands for the validation of alternative methods to reduce the resort to animal experimentation. Methods that evaluate reproductive toxicity are among those requiring the largest use of animals. Presently, no validated in vitro alternative exists for the assessment of reproductive toxicity. Mammalian sperm are sensitive targets of DNA-reactive chemicals, which form premutagenic adducts. Here, we propose a new method based on comet assay to detect DNA damage induced by potential germ cell mutagens in bull sperm available from assisted reproduction practices. In somatic cells, chemical-induced adducts can be revealed by comet assay that detects DNA breaks produced during adduct repair. Mature sperm, however, are devoid of repair enzymes, and adducts are processed only after fertilization. For this reason, comet assay is not sensitive to detect DNA lesions induced in sperm by most chemicals. To overcome such limitation, we developed a modified comet assay based on the addition of a protein extract from HeLa cells to agarose-embedded sperm on microscopic slides. To test the method, sperm were treated in vitro with methyl methanesulfonate (MMS) or melphalan (MLP) and comet assay was conducted both with and without protein supplementation. No effect of MMS or MLP was detected without protein supplementation; on the contrary, a clear-cut dose-dependent effect was measured after addition of the cell extract. These results represent a proof of concept of a novel in vitro mutagenicity test on sperm that could offer a promising approach to complement previously validated in vivo germ cell genotoxicity assays.     

Changes in pulmonary function test and cardio-pulmonary exercise capacity in COPD patients after lobar pulmonary resection.

OBJECTIVE: Pulmonary Function Tests (PFT) and Cardio-Pulmonary Exercise Testing (C-PET) are useful to evaluate operability in functionally compromised patients. Although modifications of PFT and C-PET after lung surgery have been widely explored, little information exists as to modifications of exercise capacity in COPD patients undergoing lung resection. We prospectively analyzed the changes in PFT and C-PET in patients with COPD after a pulmonary lobar resection. METHODS: From January 2003 to March 2004 all patients scheduled for lung resection were considered for participation in the study protocol. Those patients with a preoperative diagnosis of COPD on PFT were explored through a C-PET. Only patients who had undergone a lobar pulmonary resection were subsequently considered; these patients had a new complete cardio-respiratory evaluation 3 months after surgery. The pre- and postoperative values compared were those of FEV1, TLC, DLCO, VO2max, and VE/VCO2. Data are expressed as mean +/- standard deviation (SD). Statistic evaluation was made using the Wilcoxon test. RESULTS: During this period 11 patients completed the study protocol. Ten patients underwent surgery for NSCLC and one for a pulmonary aspergilloma. Nine lobectomies and two bilobectomies were performed. In the study population, the preoperative mean value of FEV1 resulted as being 53% (SD+/-20) of the predicted mean value, that of TLC 120% (SD+/-35) and that of DLCO 65% (SD+/-27). The preoperative mean value of VO2max resulted as being 17.8 ml/Kg/min (SD+/-3.25) and mean VE/VCO2 resulted as being 35.7 (SD+/-4). Three months after surgery the measured mean value of FEV1 was 53% (SD+/-18), that of TLC was 99% (SD+/-24) and that of DLCO 52% (SD+/-18). The mean value of VO2max resulted as being 14.1 ml/Kg/min (SD+/-3.04) and that of VE/VCO2 was 42.5 (SD+/-12.8). Statistical analysis of PFT values showed that FEV1 and DLCO were not significantly modified (P > 0.05); in contrast, TLC had significantly decreased (P = 0.008). VO2max had significantly decreased (P = 0.004) and VE/VCO2 had significantly increased (P = 0.018). CONCLUSIONS: Three months after a lobar pulmonary resection, patients with COPD were found to have a significant decrease in exercise tolerance. PFT alone can underestimate the postoperative loss of exercise capacity through exercise.     

Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.     

Nasal lavage leukotrienes in infants with RSV bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys-LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease.     

Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.