Abdominal wall hernia surgery: prosthetic materials

Treatment of abdominal hernia has been revolutionised by using new prostheses. Reduction of tissue tension, elimination of wall defects and lowering of recurrences are the key aspects of the success of these devices. In Italy, prostheses are widely used. Marketing enquires show percentages of prosthesis use of over 80% for the treatment of primitive hernias and as much as 100% for recurrences. It is strongly recommended that randomised prospective studies be carried out in order to establish the advantages and disadvantages of the various techniques. Moreover, an international classification should be considered so that all surgeons can use the same language and compare their results.     

Ontogeny of ( -Ala)-deltorphin I-like immunoreactive neurones in foetal rat brain

Foetal rat brain from embryonic day (ED) 12–22 was immunohistochemically studied to describe the time of first appearance and further distribution patterns of ( -Ala²)-deltorphin-I-immunoreactive (DADTI-IR) nerve elements. The primary antiserum used in this study was a polyclonal antibody against DADTI previously used in adult and postnatal rat brain mapping. DADTI-IR nerve elements first appeared in the neuroepithelium of ventral mesencephalon on ED 13. From there, positive cell bodies migrated towards the mantle layer until they invaded the whole ventral mesencephalic tegmentum. They then reached their definitive position, corresponding to a subpopulation of the A8, A9 and A10 dopaminergic neurones that had been constantly observed also in the adult age. From ED 15–17, DADTI-positive nerve fibres appeared in the medial forebrain bundle, the neostriatum anlage, the accumbens nucleus, the olfactory tubercle, the fasciculus retroflexus, and the prefrontal cortex. All these locations have also been found in adult rats. From ED 14 onwards, transient DADTI-IR somata and nerve fibres were observed in retinal neuroepithelium, optic pathways as far as the superior colliculus, CA3 hippocampal field, reticular formation in the medulla oblongata. All these locations gradually disappeared either before birth (medulla oblongata) or within the first 3 weeks after birth. These results suggest that the DADT-like molecule recognised by our antibody has during the embryonic development a regulatory function in neuronal growth and differentiation.     

Has lung cancer in the elderly different characteristics at presentation?

Lung cancer is the first cause of cancer death for males aged > or =35 years, and the second for females aged between 35 and 70 years. Elderly patients seem to have the worst performance status (PS) and earlier stage of disease at diagnosis. We analyzed data concerning 1,035 patients with lung cancer referred to the National Cancer Institute of Naples. The variables considered in the analysis were: gender; type of cancer [small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC)]; ECOG (Eastern Cooperative Oncology Group) PS, the stage of disease at diagnosis, the histological type, age at diagnosis. In order to better assess the relevance of age at diagnosis in lung cancer patients we categorized the age into two groups (young < or =70; old >70 years). The statistical analyses were performed using chi2 trend test with corresponding p-value and odds ratios (OR) for the examined variables, with a corresponding 95% confidence interval. These were derived using multiple logistic regression, fitted by the maximum likelihood method. For all the 1035 patients the risk between the age at diagnosis and the performance status was not statistically significant (OR=1.1, 95%CI 0.8-1.5). We repeated the same risk distinguishing the histological type and we analyzed the performance status for the SCLC (OR=1.0, 95%CI 0.4-2.5) and the stage at diagnosis (OR=1.0, 95%CI 0.4-3.0), without any significant difference. Our study showed that elderly patients with lung cancer do not seem to have different characteristics at presentation, particularly related to stage of disease, PS and histology, as compared to their younger counterpart. Other characteristics such as type and number of co-morbidities and organ function differ in the two groups of populations.     

Ontogeny, distribution and amine/peptide colocalization of chromogranin A- and B-immunoreactive cells in the chicken gizzard and antrum

The ontogeny and the distribution of chromogranin A (CgA)- and chromogranin B (CgB)-immunoreactive endocrine cells was studied in the chicken gizzard and gizzard-duodenal junction (also called pylorus or antrum) during embryonic and postnatal life. The same tissue sections were then double-immunostained to identify the CgA- and CgB-immunoreactive cells, with a panel of polyclonal antibodies raised against main gut amine/peptides. In the gizzard, positive cells were observed only in its two diverticula (proximal and distal caeca), where the first CgA- and CgB-immunoreactive cells were found on day 12 of incubation. They always remained moderate in number and co-stored mainly serotonin, gastrin/CCK and neurotensin. A few also co-stored somatostatin, but only during the embryonic period. Others co-stored PYY, but only after hatching. Co-localization with motilin was rare and never occurred with bombesin. In the chicken antrum, the first CgA- and CgB-immunoreactive cells were observed on day 12 of incubation and soon reached very high numbers. Antral positive cells showed almost the same co-localization pattern as the gizzard diverticula. Despite their high chromogranin content, the antral cells had weak argyrophilia, whereas in the gizzard diverticula the two staining patterns corresponded.     

Thapsigargin modulates osteoclastogenesis through the regulation of RANKL-induced signaling pathways and reactive oxygen species production.

The mechanism by which TG modulates osteoclast formation and apoptosis is not clear. In this study, we showed a biphasic effect of TG on osteoclast formation and apoptosis through the regulation of ROS production, caspase-3 activity, cytosolic Ca2+, and RANKL-induced activation of NF-kappaB and AP-1 activities. INTRODUCTION: Apoptosis and differentiation are among the consequences of changes in intracellular Ca2+ levels. In this study, we investigated the effects of the endoplasmic reticular Ca2+-ATPase inhibitor, thapsigargin (TG), on osteoclast apoptosis and differentiation. MATERIALS AND METHODS: Both RAW264.7 cells and primary spleen cells were used to examine the effect of TG on RANKL-induced osteoclastogenesis. To determine the action of TG on signaling pathways, we used reporter gene assays for NF-kappaB and activator protein-1 (AP-1) activity, Western blotting for phospho-extracellular signal-related kinase (ERK), and fluorescent probes to measure changes in levels of intracellular calcium and reactive oxygen species (ROS). To assess rates of apoptosis, we measured changes in annexin staining, caspase-3 activity, and chromatin and F-actin microfilament structure. RESULTS: At concentrations that caused a rapid rise in intracellular Ca2+, TG increased caspase-3 activity and promoted apoptosis in osteoclast-like cells (OLCs). Low concentrations of TG, which were insufficient to measurably alter intracellular Ca2+, unexpectedly suppressed caspase-3 activity and enhanced RANKL-induced osteoclastogenesis. At these lower concentrations, TG potentiated ROS production and RANKL-induced NF-kappaB activity, but suppressed RANKL-induced AP-1 activity and had little effect on ERK phosphorylation. CONCLUSION: Our novel findings of a biphasic effect of TG are incompletely explained by our current understanding of TG action, but raise the possibility that low intensity or local changes in subcellular Ca2+ levels may regulate intracellular differentiation signaling. The extent of cross-talk between Ca2+ and RANKL-mediated intracellular signaling pathways might be important in determining whether cells undergo apoptosis or differentiate into OLCs.     

ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda

The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non-glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations have been implicated in Mal de Meleda. In this study we show by immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the protein product of the ARS Component B gene) is localized to human skin, exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is detected in human plasma and urine. In the mouse, expression is evident in skin, eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. The tissue localization and the association with Mal de Meleda suggest that ARS Component B and its protein product SLURP1 are implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin.     

A phase II study of dose‐dense and dose‐intense ABVD (ABVDDD‐DI) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma

We explored activity and safety of a dose‐dense/dose‐intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVD_DD‐DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two‐stage Bryant‐Day Phase II study to receive six cycles of ABVD_DD‐DI without consolidation radiotherapy. Cycles were supported with granulocyte colony‐stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m²; first four cycles only). Co‐primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event‐free (EFS) and disease‐free survival (DFS). All patients received the four doxorubicin‐intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose‐intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five‐year EFS and DFS was 88·3% and 93·7%, respectively. ABVD_DD‐DI regimen was well‐tolerated and ensured substantial CR and EFS rates without radiotherapy.     

Heroin sensitization as mapped by c-Fos immunoreactivity in the rat striatum

Immunohistochemistry was used to map the induction of c-Fos protein in the forebrain of rats treated with heroin. Acute injection of heroin to drug-naive rats caused significant induction of c-Fos protein in the nucleus accumbens shell, whereas the same dose of heroin given to drug-sensitized rats significantly increased c-Fos immunoreactivity in the dorsomedial caudate-putamen. These results show that the heroin-induced pattern of c-Fos protein in the rat striatum differs according to the rat's drug history. These findings may represent a neural correlate of the motor components of heroin sensitization.