Transversus abdominis plane block for analgesia after Cesarean delivery. A systematic review.

Cesarean delivery is a major surgical procedure, after which a woman can experience substantial postoperative discomfort or pain. Inadequate postoperative analgesia is one of the most common reasons for poor patient satisfaction following cesarean delivery. Although spinal or systemic opioids are currently the gold standard to achieve effective analgesia, they are often associated with side effects. In the last few years there has been growing interest in abdominal plane blocks, with promising data on their efficacy. The transversus abdominis plane (TAP) block is a regional analgesic technique which is gaining acceptance in postoperative analgesia for lower abdominal surgeries. In this systematic review of articles published as of 31 December 2013, we searched the principal medical databases for randomized controlled trials that assessed the efficacy of ultrasound (US)-guided TAP block following cesarean delivery and reported on postoperative opioid consumption and pain score, opioid-related side-effects and patient satisfaction. Although controversy surrounds the utility of US-guided TAP block in cesarean section, evidence suggests that when correctly executed as part of a multimodal analgesic regimen, TAP block may reduce postoperative opioid consumption and opioid-related side effects, improving postoperative pain control and patient satisfaction. Further studies are necessary to explore this field of research.

A new chance to maintain remission induced by anti-TNF agents in rheumatoid arthritis patients: CYnAR study II of a 12-month follow-up.

The advent of biological therapies represented the beginning of a new era in the therapy of Rheumatoid Arthritis (RA), as demonstrated in several studies, but still many questions about their safety, especially in long term use, and correct administration time remain unanswered. Once remission is achieved, the orientation of clinicians regarding the maintenance of biological therapy or the switch to another immunosuppressive therapy is still uncertain. In our previous study 21 patients affected by RA who reached remission by the use of a combined therapy of anti-TNF drugs and methotrexate (MTX) underwent CyA-MTX combination therapy for maintaining remission state and were evaluated during a 6-month follow-up. The present study aims to investigate these data by a longer follow-up (12 months) and on a larger population. Fifty-three RA patients, with a disease duration of less than 3 years and DAS28<3.2 that reached a level of low disease activity within 6-8 months from the beginning of anti-TNF and methotrexate therapy, were enrolled in the study. By the suspension of anti-TNF therapy, patients underwent A-Cyclosporine (2-3 mg/kg/day) and methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation rate (ESR), C Reactive Protein (CRP) were all tested at time 0 and every 2 months after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and methotrexate therapy, as well as liver and kidney profiles. Side effects were also recorded. Of 53 patients, 50 completed the study with a 12-month follow-up. Twenty-one (42%) patients maintained clinical parameters within low disease activity values at 12 months, while 29 (58%) patients showed an increase in DAS28 and other parameters: 16 (32%) patients at the 6-month control, 13 (26%) patients at the 12-month control. Our data show that 42% of the patients undergoing A-Cyclosporin and Methotrexate therapy maintained low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agents in rheumatoid arthritis patients? (Cynar pilot study).

Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6-8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2-3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6-8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

A new technical contribution for ultrasound-guided injections of sacro-iliac joints.

INTRODUCTION: Sacroiliac joint (SIJ) represents a difficult location for local therapies, as intra-articular injections may be hard to execute, especially in particular conditions such as chronic inflammatory diseases. However, in selected patients, local therapies may be considered. Some recent studies demonstrated the feasibility of ultrasound (US)-guided injection of SIJ, but still a complete explanation and definition of the technique is needed. MATERIALS AND METHODS: Seven patients, four males and 3 females, affected by mono or bilateral sacroiliitis entered the study. Each patient received 40 mg of acetonide triamcinolone for each SIJ, intra articular (IA) US-guided injection. The technical originality proposed in this study consists in the spinal needle insertion in the middle of the cranial long side of the linear transducer with an orientation of about 10 degrees, determining shorter needle insertion for reaching joint space and consequently probably granting lesser pain and traumatism for patients. RESULTS: A total of 22 injections was performed. The longer follow-up time obtained was 18 months in 3 patients. All patients reached at least a 6 month follow-up. All patients reported an amelioration in pain that lasted for at least 6 months. No systemic adverse events were reported or observed. Complete visualization of SIJ and of needle placement was performed by US imaging, while compound proper injection was also visualized by Color-Doppler US imaging. DISCUSSION: Actually, sacroiliac joint intraarticular injections are often performed under fluoroscopy or Computerized Tomography guidance. Such techniques present several limitations, especially for repeated injections, such as the use of ionizing radiations, the need of a contrast agent and the direct and indirect costs connected. US guidance in IA SIJ injections may represent an easily repeatable imaging technique for needle placement and a precious tool for detecting inflammatory activity of the joint.

The safety of anti-TNF agents in the elderly.

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patients twenties or thirties, they usually persist for the duration of the patients life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

Viscosupplementation: a suitable option for hip osteoarthritis in young adults.

INTRODUCTION: Young adult hip osteoarthritis (OA) is a noteworthy problem, although rarer than the elderly form of the disease, causing limitations in social and working activities and prospects. Treatment options are scarce and surgical procedures, frequently necessary, imply the major drawback of revising the prostheses periodically, whereas chronic nonsteroidal anti-inflammatory drugs (NSAID) consumption may provoke side effects. To explore alternative options to both surgery and long-term NSAID use, especially in the case of young patients, viscosupplementation seems to appear as an appropriate tool to relieve pain, ameliorate the function and delay surgery. AIM OF THE STUDY: In this study we tackle the issue of the use of hyaluronic acid (HA) injections in young adults with symptomatic hip OA. RESULTS AND CONCLUSIONS: These data, collected from 78 young patients, show that viscosupplementation is a safe procedure, and may provide significant relief from pain and functional recovery. Larger controlled studies are needed to establish otpimal treatment strategies and clinical factors predictive of treatment response.

Mixed panniculitis responding to cyclosporin-A with a 12-month follow-up: a case report.

Panniculitides represent a heterogeneous group of inflammatory diseases involving subcutaneous fat. Subcutaneous fat is normally organized into adipose cells, adipocytes, and septa of connective tissue. The inflammation involving such tissues can be more represented in septa (septal panniculitis) or in lobules (lobular panniculitis) or be equally distributed in both (mixed panniculitis). A bioptical study is necessary in order to discern between different forms. Vascular involvement is also different in such diseases, as it can interest arteries, or veins, or both. Different grades of fat necrosis can also be observed, such as adipocytes without nuclei, lipophagic necrosis, liquefactive fat necrosis, microcystic fat necrosis, ischaemic fat necrosis. Panniculitis can be idiopathic or secondary to other diseases such as systemic sclerosis, rheumatoid arthritis, systemic erithematous lupus and many others. Therapies usually vary on the single patient but the general orientation leads to the use of immunosuppressive drugs such as thalidomide, corticosteroids, cyclosporin-A, hydroxychloroquine and cyclophosphamide. We report a case of a 19-year-old female affected by primary mixed panniculitis, associated with fever and deep asthenia, that resolved in a few weeks and was maintained with oral cyclosporin-A.

[Correlation between radiologic and ultrasonographic patterns and clinical manifestations in symptomatic hip osteoarthritis]. / Correlazione tra quadro clinico e patterns radiologici ed ecografici in pazienti affetti da artrosi sintomatica dell'anca.

Increasing amounts of data have recently been published regarding ultrasonographic (US) findings of osteoarthritic joints, but very few data concern hip joints. In the current study we described US patterns concerning 490 patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra-articular injections of hyaluronic products under US guidance. All patients were studied by US and X-ray of hip, clinical evaluation was assessed by the followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and Global Patient Assessment. US findings were summarized in four main patterns, effusion and synovial proliferation were also detected. The aim of this study was to correlate US findings with clinical assessment and radiographic findings (according to Kellgren-Lawrence classification). Pearson's r correlation coefficient were computed and come out significant and positive between X ray and US patterns and between clinical indexes and US patterns. Also the correlation between K-L score and US patterns showed a significant positive correlation indicating that higher K-L scores are associated with increasing abnormal US findings. Our data suggest that ultrasonography of the hip may give useful information about the state of synovial membrane, synovial fluid, joint margins and bone profile in hip OA. Further studies are needed to evaluate their prevalence in hip OA symptomatic and not-symptomatic patients and their correlation to treatment outcome.

Is laparoscopic bladder diverticulectomy after transurethral resection of the prostate safe and effective? Comparison with open surgery.

PURPOSE: In a retrospective nonrandomized study, we compared our experience with transurethral resection of the prostate (TURP) plus sequential laparoscopic bladder diverticulectomy with a series of combined open bladder diverticulectomies with transvesical prostatectomy. PATIENTS AND METHODS: We considered 12 consecutive patients (group A) having 16 diverticula who underwent sequential TURP and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group B) having 13 diverticula who underwent open bladder diverticulectomy and transvesical prostatectomy. We evaluated the size and position of the diverticulum, adenoma volume, operative time, postoperative hemoglobin variations, analgesia requirement, complications, postoperative hospital stay, and uroflowmetry results. RESULTS: No statistically significant differences existed between the groups in adenoma volume or diverticulum size or position. However, a significantly longer operative time was recorded in group A. The endolaparoscopic approach proved to be statistically superior to open surgery regarding blood loss, postoperative analgesia requirement, and hospital stay. No intraoperative complications were recorded. In addition, no statistically significant difference was found in uroflowmetry results. CONCLUSIONS: In our experience, the endolaparoscopic approach has proved to be safe, effective, and minimally invasive and therefore superior to transvesical prostatectomy and open bladder diverticulectomy. Its only disadvantage is the longer operative time.

Dropout rates with olanzapine or risperidone: a multi-centre observational study.

OBJECTIVE: In patients with schizophrenia, risperidone and olanzapine are the two most commonly used atypical anti-psychotics. A recent meta-analysis based on randomized trials suggests that, in the long term, olanzapine can have a lower frequency of treatment discontinuation (or dropout) in comparison with risperidone. To better test this hypothesis, our observational study was aimed at assessing whether or not this advantage of olanzapine versus risperidone could be confirmed in a patient series examined in an observational setting. METHODS: Our study was based on a retrospective multi-centre observational design. We collected the following information from each patient: demographic characteristics; current anti-psychotic treatment (olanzapine or risperidone, under the condition of a stable therapy over months -1 to -4); cumulative dose of the drug; previous anti-psychotic treatment (during months -5, -6, -7 and/or, when available, also before month -7); daily dose and treatment duration. Our primary analysis traced back the patient's history from the date of enrollment retrospectively up to month -7. The secondary analysis followed-up the patient's history prior to month -7, thus extending this retrospective recording as long as possible (depending on what information was actually available for individual patients). RESULTS: The patients were enrolled from 31 institutions. In our primary analysis (months -1 to -7), a total of 144 patients were included; in this subgroup treated with olanzapine or risperidone as initial drug ( n=94), we observed 4 of 54 switches from olanzapine to risperidone and 11 of 40 switches from risperidone to olanzapine ( P=0.01). A total of 454 patients were enrolled in our secondary analysis (from month -1 up to month -73); the same comparison showed 9 of 236 switches from olanzapine to risperidone and 17 of 150 switches from risperidone to olanzapine ( P=0.004). CONCLUSION: Our analysis confirms the results of a recent meta-analysis and shows that olanzapine might imply a lower risk of dropout than risperidone.

Postmenopausal osteoporosis and hormone replacement therapy.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Postmenopausal osteoporosis is a major public health problem. Estrogen deficiency is a key factor in the pathogenesis of postmenopausal osteoporosis. Among the several types therapeutic intervention in osteoporosis, hormone replacement therapy (HRT) has traditionally been seen as the gold standard method of preventing osteoporotic fractures among postmenopausal women.The estrogenic effect on bone is dose-dependent. For oral therapy, studies have demonstrated that doses of 0.625 mg of conjugated equine estrogen and 2 mg of micronized estradiol prevent postmenopausal bone loss. Percutaneous 17 beta-estradiol prevents skeletal bone loss as effectively as oral HRT. Although the greatest benefits from HRT in terms of bone sparing effects can be obtained shortly after the menopause, the literature contains clear evidence that HRT prevents bone loss in all stages of postmenopausal life. However, estrogen therapy must be long-term, possibly lifelong, to have any lasting impact on bone health. One strategy to improve long term continuation of HRT is to reduce the dosage of estrogen and the consequent side-effects of the higher dose HRT. Various studies have assessed the efficacy of low-dose HRT (LD-HRT) as well as the standard dose HRT in the prevention of osteoporosis in postmenopausal women. LD-HRT may enhance patient acceptability and continuation, ensuring adequate bone protection and menopausal symptoms control, and given physicians the possibility to personalize the doses on the basis of each individual patient's needs.

Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists.

In the present work we examined the involvement of selected P2X receptors for extracellular ATP in the onset of neuronal cell death caused by glucose/oxygen deprivation. The in vitro studies of organotypic cultures from hippocampus evidenced that P2X2 and P2X4 were up-regulated by glucose/oxygen deprivation. Moreover, we showed that ischemic conditions induced specific neuronal loss not only in hippocampal, but also in cortical and striatal organotypic cultures and the P2 receptor antagonists basilen blue and suramin prevented these detrimental effects. In the in vivo experiments we confirmed the induction of P2X receptors in the hippocampus of gerbils subjected to bilateral common carotid occlusion. In particular, P2X2 and P2X4 proteins became significantly up-regulated, although to different extent and in different cellular phenotypes. The induction was confined to the pyramidal cell layer of the CA1 subfield and to the transition zone of the CA2 subfield and it was coincident with the area of neuronal damage. P2X2 was expressed in neuronal cell bodies and fibers in the CA1 pyramidal cell layer and in the strata oriens and radiatum. Intense P2X4 immunofluorescence was localized to microglia cells. Our results indicate a direct involvement of P2X receptors in the mechanisms sustaining cell death evoked by metabolism impairment and suggest the use of selected P2 antagonists as effective neuroprotecting agents.

Sequential transurethral resection of the prostate and laparoscopic bladder diverticulectomy: comparison with open surgery.

OBJECTIVES: To compare our experience with transurethral resection of the prostate and sequential laparoscopic bladder diverticulectomy with a previous series of combined open bladder diverticulectomy and transvesical prostatectomy. METHODS: We compared the data of 10 consecutive patients (group 1) who underwent sequential transurethral resection of the prostate and transperitoneal laparoscopic bladder diverticulectomy and 13 consecutive patients (group 2) who underwent traditional combined open bladder diverticulectomy and transvesical prostatectomy. The following parameters were considered: size and position of the diverticulum, transrectal ultrasound adenoma volume, operative time, postoperative hemoglobin variations, analgesic requirement, complications, postoperative hospital stay, and urinary flowmetry. RESULTS: No statistically significant differences existed between the two groups either for diverticulum size (6.8 versus 7.2 cm) or diverticula position. A significant difference was observed in the operative time (247 minutes for group 1 versus 136 minutes for group 2, P <0.0001), mean postoperative hemoglobin decrease (2.6 g/dL for group 1 and 3.9 g/dL for group 2, P = 0.001), analgesic requirement (1.3 ampoules of buprenorphine cloritrate for group 1 versus 1.8 ampoules for group 2, P = 0.45), and postoperative hospital stay (3 days for group 1 versus 9.6 days for group 2, P <0.0001). No statistically significant difference was recorded for control flowmetry. No intraoperative complications were recorded for the two groups. CONCLUSIONS: In our series, sequential transurethral resection of the prostate and transperitoneal laparoscopic diverticulectomy for large diverticula proved to be a safe, effective, and minimally invasive procedure, despite the longer operative times compared with transvesical prostatectomy and open bladder diverticulectomy.

Transactivation of the epidermal growth factor receptor in endothelin-1-induced mitogenic signaling in human ovarian carcinoma cells.

Endothelin (ET)-1 is produced in ovarian carcinoma cells and is known to act through ET(A) receptors as an autocrine growth factor in vitro and in vivo. In OVCA 433 human ovarian carcinoma cells, ET-1 caused phosphorylation of the epidermal growth factor receptor (EGF-R) that was accompanied by phosphorylation of Shc and its recruitment complexed with Grb2. These findings suggested that an EGF-R/ras-dependent pathway may contribute to the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) 2 and mitogenic signaling induced by ET-1 in these cells. Specific inhibition of EGF-R kinase activity by tyrphostin AG1478 prevented ET-1-induced transactivation of the EGF-R, as well as Shc phosphorylation and recruitment with Grb2. Furthermore, ET-1-induced activation of Erk 2 was partially inhibited by tyrphostin AG1478. In accord with this finding, the mitogenic action of ET-1 in OVCA 433 cells was also significantly reduced by a concentration of tyrphostin AG1478 that abolished the growth response of EGF-stimulated cells. Inhibition of protein kinase C activity, which contributes to the proliferative action of ET-1 in OVCA 433 cells, had no effect on the activation of Erk 2 by ET-1, which suggests that this effect of protein kinase C does not involve ras-independent activation of Erk 2. Inhibition by wortmannin of PI3-kinase activity, which has been implicated in ET-1 and other G protein-coupled receptor (GPCR)-mediated signaling pathways, reduced Erk 2 activation by ET-1 but had no effect on ET-1-induced EGF-R and Shc phosphorylation. These findings indicate that ET-1-induced stimulation of Erk 2 phosphorylation, and mitogenic responses in OVCA 433 ovarian cancer cells are mediated in part by signaling pathways that are initiated by transactivation of the EGF-R.

SDF-1alpha-mediated modulation of synaptic transmission in rat cerebellum.

The functional expression of the seven-transmembrane domain G protein-coupled chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by staining with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium responses to the physiological agonist stromal-derived cell factor-1alpha (SDF-1alpha) in both cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar slices. Cerebellar glial, granule and Purkinje cells showed a pronounced staining for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients elicited by the application of SDF-1alpha, both in cell bodies and in neuronal processes. Whole-cell patch-clamped PNs in cerebellar slices responded to SDF-1alpha application by a slow inward current followed by an increase of both intracellular Ca2+ level and spontaneous synaptic activity. In particular, the SDF-1alpha-induced slow inward current was considerably reduced by ionotropic glutamate receptor blockers, but developed fully in a medium in which synaptic transmission was inhibited, indicating that this current might be, at least in part, mediated by extrasynaptic glutamate, possibly released from the surrounding glial and/or nerve cells. Taken together, these findings indicate a functional involvement of CXCR-4 in the modulation of synaptic transmission, adding another member to the repertoire of the chemokine receptors exerting a neuromodulatory role in the cerebellum.

The chemokine growth-related gene product beta protects rat cerebellar granule cells from apoptotic cell death through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors.

Cultured cerebellar granule neurons are widely used as a cellular model to study mechanisms of neuronal cell death because they undergo programmed cell death when switched from a culture medium containing 25 mM to one containing 5 mM K(+). We have found that the growth-related gene product beta (GRObeta) partially prevents the K(+)-depletion-induced cell death, and that the neuroprotective action of GRObeta on granule cells is mediated through the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type of ionotropic glutamate receptors. GRObeta-induced survival was suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, which is a specific antagonist of AMPA/kainate receptors; it was not affected by the inhibitor of N-methyl-D-aspartate receptors, 2-amino-5-phosphonopentanoic acid, and was comparable to the survival of granule cells induced by AMPA (10 microM) treatment. Moreover, GRObeta-induced neuroprotection was abolished when granule cells were treated with antisense oligonucleotides specific for the AMPA receptor subunits, which significantly reduced receptor expression, as verified by Western blot analysis with subunit-specific antibodies and by granule cell electrophysiological sensitivity to AMPA. Our data demonstrate that GRObeta is neurotrophic for cerebellar granule cells, and that this activity depends on AMPA receptors.

The growth-related gene product beta induces sphingomyelin hydrolysis and activation of c-Jun N-terminal kinase in rat cerebellar granule neurones.

The growth-related gene product beta (GRObeta) is a small chemoattractant cytokine that belongs to the CXC chemokine family, and GRObeta receptors are expressed in the brain, including the cerebellum. We demonstrate that rat cerebellar granule neurones express the GRObeta receptor CXCR2. We also show that, in addition to the known stimulation of a phosphoinositide-specific phospholipase C, GRObeta activates both neutral (N-) and acidic (A-) sphingomyelinases (SMase) and the stress-activated c-Jun N-terminal kinase 1 (JNK1). Although both exogenous ceramide and bacterial SMase stimulate JNK1, GRObeta-induced JNK1 activation is an event probably independent of ceramide generated by A-SMase, since it is maintained in the presence of compounds that block A-SMase activity. This is the first report on the activation of the SMase pathway by chemokines.

Simultaneous influenza and pneumococcal vaccination in elderly individuals.

The study was performed to evaluate the effects of influenza and pneumococcal vaccines administered alone or in combination. 124 elderly subjects living in community were vaccinated either with influenza split vaccine or with pneumococcal 23-valent or with both vaccines at the same time in different sites. Sera were tested for hemoagglutination inhibiting antibodies for influenza and for antibodies against 23-valent vaccine for streptococcus pneumoniae. No side effects were observed in the vaccinated population. Serological results indicated that influenza vaccine increased significantly antibody levels. No difference was observed between the group which received influenza vaccine alone and that which received influenza and pneumococcal vaccines associated, considering either G.M.T or the percentages of protected individuals or the percentages of subjects who seroconverted. When pneumococcal vaccine was administered at the same time with influenza vaccine, there was a not statistically significant reduction in both mean antibody concentration and mean fold increase. It is concluded that the simultaneous administration of influenza and pneumococcal vaccines to elderly individuals, including subjects at risk, is safe, effective and economically advantageous.

Immune response to a booster dose of enhanced potency inactivated polio vaccine administered in association with HBV vaccine in adolescents.

The immunogenicity and reactogenicity of a booster dose of enhanced potency inactivated polio vaccine (EIPV) were evaluated in 492 healthy 12 year old adolescents. The booster was administered at the same time as the HBV vaccine compulsory in Italy at this age. Blood samples and questionnaires on reactogenicity were collected over 9 months. Analysis of pre-vaccination immunity showed that 97.4% of the subjects were protected against all polio types, 1.9% were negative for two polio types and 0.6% for one. After vaccination 98.4% of the vaccinees showed a significant increase ( > or = 4 times) of antibody titre; the geometric mean titres (GMT) were markedly higher than before vaccination, particularly for poliovirus type 3. The polio booster dose did not affect HBV vaccination. An anti-HBs response > 10 mIU ml-1. (GMT = 2951 mIU ml-1) was observed in 781 (98.6%) of 792 vaccinees (492 given EIPV+HBV and 300 given only HBV) 9 months later. Only mild local and rare general reactions were noted for both the vaccines studied. These data confirm the suitability and efficacy of an EIPV booster dose and HBV vaccination in adolescents.

Structural and antifungal properties of a pathogenesis-related protein from wheat kernel.

We have purified and characterized a protein from the water-soluble fraction of wheat kernel (Triticum aestivum cv. S. Pastore) consisting of a single polypeptide chain blocked at its N-terminus by a pyroglutamate residue; the complete amino acid sequence has been determined by automated sequence analysis performed on peptide fragments obtained by enzymatic hydrolyses of the protein. Homology studies have shown that this protein is very similar (97% sequence identity) to the previously characterized wheatwin1 as well as to other members of the pathogenesis-related (PR) proteins of class 4; in analogy with wheatwin1, we have termed this protein wheatwin2. Both wheatwin1 and wheatwin2 have specific antifugal activity toward the wide-host-range pathogen Botrytis cinerea and the wheat-specific pathogenic fungi of wheat Fusarium culmorum and Fusarium graminearum of groups 1 and 2. On the basis of their structural and functional properties, wheatwin1 and wheatwin2 can be classified as members of the PR4 protein family; this represents the first report concerning the presence of this kind of protein in wheat.