Thoughts and concerns of patients at hospital discharge after lumbar spine surgery. A qualitative study.

PURPOSE: The increased rate of surgical interventions point to the necessity to investigate the patient's experience from a biopsychosocial perspective. The aim of this study was to investigate the thoughts and concerns of patients undergoing spinal surgery for lumbar degenerative disease at the time of their discharge from hospital. METHODS: Semi-structured interviews were conducted with 28 patients. The questions investigated possible concerns associated to discharging them home. A content analysis was performed by a multidisciplinary group to identify the main themes that emerged from the interviews. RESULTS: The patients were satisfied with the surgeons' preoperative explanations and description of expected prognosis. However, they were disappointed with the lack of information at hospital discharge, in particular regarding practical and behavioral recommendations. The patients expressed clear concerns about being left alone to deal with possible complications or difficulties they may encounter when returning home. CONCLUSION: This study underlined the patients' need for a comprehensive psychological guidance and possibly a person of reference during the post-operative process. Discussing discharge with the patient was emphasized as an important issue to improve patients' compliance to the recovery process itself. Putting these elements into practice should help spine surgeons to manage better hospital discharge.IMPLICATIONS FOR REHABILITATIONA comprehensive discussion with the patient at the time of hospital discharge is clearly stressed as an important issue to improve patients' adherence to the recovery process.The patients complained of a lack of information when returning home, in particular regarding practical and behavioral recommendations.The patients expressed clear concerns about possible complications or difficulties they may encounter when returning home and they expressed their need to know whom they can contact for help if needed.A better understanding of the thoughts and concerns of patients undergoing spinal surgery at the time of their discharge from hospital should help spine surgeons to improve the management of hospital discharge and the post-operative recovery.

Conservative vs. surgical approach for degenerative meniscal injuries: a systematic review of clinical evidence.

OBJECTIVE: Analyzing the available evidence by comparing the role of arthroscopic surgery and conservative treatment in the management of degenerative meniscopathy. MATERIALS AND METHODS: A literature search was carried out on the PubMed, EMBASE, Scopus, and PEDro databases in May 2019 to identify all the randomized controlled trials (RCTs) comparing arthroscopic surgery to conservative management of painful but stable degenerated menisci. The quality of the RCTs was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 10 studies, including 1525 patients and dealing with conservative treatment vs. arthroscopic surgery were included in this review. In eight studies the effectiveness of exercise therapy was compared to surgery; in one study the effectiveness of intra-articular steroid injection was compared to surgery; in one study the effectiveness of placebo surgery was compared to partial meniscectomy. In all studies, no significant inter-group difference in terms of knee pain and knee function were observed at any follow-up evaluation. CONCLUSIONS: Degenerative meniscal tears, without symptoms of locking and catching, can be successfully managed by a proper regimen of physical therapy as a first line treatment. Surgical approach might be considered in case of poor response after conservative treatment.

The natural compound berberine positively affects macrophage functions involved in atherogenesis.

BACKGROUND AND AIMS: We investigated the effect of berberine (BBR), an alkaloid showing antiatherogenic properties beyond the cholesterol lowering capacity, on macrophage cholesterol handling upon exposure to human serum and on macrophage responses to excess free cholesterol (FC) loading. METHODS AND RESULTS: Mouse and human macrophages were utilized as cellular models. Cholesterol content was measured by a fluorimetric assay; cholesterol efflux, cytotoxicity and membrane FC distribution were evaluated by radioisotopic assays. Monocyte chemotactic protein-1 (MCP-1) secretion was measured by ELISA; membrane ruffling and macropinocytosis were visualized by confocal microscopy. Exposure of cholesterol-enriched MPM to serum in the presence of 1 µM BBR resulted in a reduction of intracellular cholesterol content twice greater than exposure to serum alone (-52%; p < 0.01 and -21%; p < 0.05), an effect not mediated by an increase of cholesterol efflux, but rather by the inhibition of cholesterol uptake from serum. Consistently, BBR inhibited in a dose-dependent manner cholesterol accumulation in human macrophages exposed to hypercholesterolemic serum. Confocal microscope analysis revealed that BBR inhibited macropinocytosis, an independent-receptor process involved in LDL internalization. Macrophage FC-enrichment increased MCP-1 release by 1.5 folds, increased cytotoxicity by 2 fold, and induced membrane ruffling; all these responses were markedly inhibited by BBR. FC-enrichment led to an increase in plasma membrane cholesterol by 4.5 folds, an effect counteracted by BBR. CONCLUSION: We showed novel potentially atheroprotective activities of BBR in macrophages, consisting in the inhibition of serum-induced cholesterol accumulation, occurring at least in part through an impairment of macropinocytosis, and of FC-induced deleterious effects.

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites.

OBJECTIVE: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. METHODS: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. RESULT: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. CONCLUSION: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.

Comparison of esophagectomy with and without thoracotomy in a low-resource tertiary care center in a developing country.

Esophageal cancer surgery is traditionally performed by a number of open surgical approaches. Open approaches require thoracotomy and laparotomy. Developments in instrumentation and optics have allowed the use of minimally invasive approaches to esophageal cancer, which had been traditionally managed by open operation. Minimally invasive surgery (MIS) avoids thoracotomy and laparotomy and results in quicker return to normal functions and less morbidity. In this prospective study, we compared the immediate surgical and oncologic outcomes of patients who have undergone MIS with those who have had open surgery. From November 1, 2003 to March 30, 2006, 62 cases of carcinoma esophagus were operated in Surgical unit 3 (MIS unit) in the institute. Out of the 62 patients, 34 (54.8%) underwent minimally invasive esophagectomy (MIE), and the remaining 28 patients (45.2%) underwent open surgery. Both operations were done by the same team of surgeons. The groups were compared in terms of perioperative outcomes, morbidity, mortality, and adequacy of oncologic excision. The average duration for MIS was 312.35 min (60-480 min), which was more than that of open group surgery whose average duration was 261.96 min (60-360 min). This difference was found to be not significant (P < 0.110). The average blood loss was 275.74 mL (200-500 mL) in minimally invasive group compared with 312.50 (200-500 mL) in open group (P-value 0.33). Four patients (11.76%) in MIS group had been converted to open surgery. Average duration of hospitalization was 11.9 (4-24) days in MIS group compared with 12.19 (5-24) days in open group (P-value 0.282). Nine (26.47%) patients in MIS group had developed major or minor morbidity. Similarly, eight (28.57%) patients in open group had morbidity. One patient each expired in each group. The morbidity and mortality rates were not statistically significant. There were four leaks (11.76%) in MIS group and three leaks (10.71%) in open group (P-value 0.85). Regarding the extent of nodal clearance, an average number of 9.5 (0-19) nodes were removed in MIS group compared with an average of 7.26 (0-12) nodes in open group (P-value 0.05). Better visibility and magnification enabled more number of lymph nodes to be removed in MIS group. MIE is oncologically safe compared with open surgery. It has almost similar postoperative course, morbidity pattern, and duration of hospital stay as open surgery. Increased duration of procedure compared with open surgery is a disadvantage of MIS, especially in the early part of learning curve.

Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia.

Maintaining genomic integrity is critical to avoid life-threatening disorders, such as premature aging, neurodegeneration and cancer. A multiprotein cascade operates at sites of DNA double-strand breaks (DSBs) to recognize, signal and repair damage. RNF168 (ring-finger nuclear factor) contributes to this emerging pathway of several E3 ubiquitin ligases that perform sequential ubiquitylations on damaged chromosomes, chromatin modifications essential for aggregation of repair complexes at the DSB sites. Here, we report the clinical and cellular phenotypes associated with a newly identified homozygous nonsense mutation in the RNF168 gene of a patient with a syndrome mimicking ataxia-telangiectasia. The mutation eliminated both of RNF168's ubiquitin-binding motifs, thus blocking progression of the ubiquitylation cascade and retention of repair proteins including tumor suppressors 53BP1 and BRCA1 at DSB sites, consistent with the observed defective DNA damage checkpoints/repair and pronounced radiosensitivity. Rapid screening for RNF168 pathway deficiency was achieved by scoring patients' lymphoblastoid cells for irradiation-induced nuclear foci containing 53BP1, a robust assay we propose for future diagnostic applications. The formation of radiation-induced DSB repair foci was rescued by ectopic expression of wild-type RNF168 in patient's cells, further causally linking the RNF168 mutation with the pathology. Clinically, this novel syndrome featured ataxia, telangiectasia, elevated alphafetoprotein, immunodeficiency, microcephaly and pulmonary failure and has implications for the differential diagnosis of autosomal recessive ataxias.

An update: salivary hormones and physical exercise.

Saliva contains cells and compounds, of local and non-local oral origin, namely inorganic, organic non-protein, protein/polypeptide, and lipid molecules. Moreover, some hormones, commonly assayed in plasma, such as steroids, are detectable in oral fluid and peptide/protein, and non-steroid hormones have been investigated. The sports practice environment and athletes' availability, together with hormone molecule characteristics in saliva and physical exercise behavior effects, confirm this body fluid as an alternative to serum. This review focuses on the relation between salivary steroids and psycho-physiological stress and underlines how the measurement of salivary cortisol provides an approach of self-report psychological indicator and anxiety change in relation to exercise performance. The correlation between salivary and plasma steroid hormone (cortisol, testosterone, and dehydroepiandrosterone (DHEA)) levels, observed during exercise, has been considered, underlining how the type, duration, and intensity of the exercise influence the salivary steroid concentrations in the same way as serum-level variations. Training conditions have been considered in relation to the salivary hormonal response. This review focuses on studies related to salivary hormone measurements, mainly steroids, in physical exercise. Saliva use in physical disciplines, as a real alternative to serum, could be a future perspective.

Chronic periaortitis associated with membranous nephropathy: clues to common pathogenetic mechanisms.

Chronic periaortitis (CP) is a rare disease hallmarked by the presence of a periaortic retroperitoneal fibro-inflammatory tissue which can often cause obstructive uropathy. CP is isolated in most cases but it may also be associated with other sclerosing inflammatory and immune-mediated diseases. We here present the case of a patient who was initially diagnosed as having CP and subsequently developed membranous nephropathy and chronic sclerosing sialoadenitis of the right parotid gland. As these conditions were all characterized by either pronounced infiltration of IgG4-positive plasma cells or marked IgG4 tissue deposition, we hypothesize that they are part of the same disease spectrum, and discuss the immune-mediated pathogenetic mechanisms potentially shared by these conditions. In particular, we consider the role of Th2-mediated immune reactions and of immunogenetic factors such as HLA genotype as common determinants of these disorders.

The glutamate transporter excitatory amino acid carrier 1 associates with the actin-binding protein alpha-adducin.

Excitatory amino acid carrier 1 (EAAC1) belongs to the family of the Na(+)-dependent glutamate carriers. Although the association between defective EAAC1 function and neurologic disease has been repeatedly studied, EAAC1 regulation is not yet fully understood. We have reported that in C6 glioma cells both the activity and membrane targeting of EAAC1 require the integrity of actin cytoskeleton. Here we show that, in the same model, EAAC1 partially co-localizes with actin filaments at the level of cell processes. Moreover, perinuclear spots in which EAAC1 co-localizes with the actin binding protein alpha-adducin are observed in some cells and, consistently, faint co-immunoprecipitation bands between EAAC1 and alpha-adducin are detected. Co-localization and partial co-immunoprecipitation of EAAC1 and adducin are still detectable after cell treatment with phorbol esters, a condition that leads to a protein kinase C (PKC)-dependent increase of EAAC1 expression on the membrane and to the phosphorylation of adducin. A co-immunoprecipitation band was also detected in protein extracts of rat hippocampus. The amount of adducin co-immunoprecipitated with EAAC1 increases after the treatment of C6 cells with retinoic acid, a differentiating agent that induces EAAC1 overexpression in this cell model. Moreover, in clones of C6 cells transfected with a hemagglutinin (HA)-tagged adducin, the bands of EAAC1 immunoprecipitated by an anti-HA antiserum were proportional to EAAC1 expression. These results suggest the existence of a pool of EAAC1 transporters associated with the actin binding protein alpha-adducin in a PKC-insensitive manner.

Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents.

BACKGROUND AND PURPOSE: The transient receptor potential ankyrin receptor 1 (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated aldehydes which seem to play a role in airway diseases. We investigated whether TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit this response. EXPERIMENTAL APPROACH: Animals were placed in a Perspex box, and cough sounds were recorded and counted by observers unaware of the treatment used. KEY RESULTS: Inhalation of two selective TRPA1 agonists, allyl isothiocyanate and cinnamaldehyde, dose-dependently caused cough in control guinea pigs, but not in those with airway sensory nerves desensitized by capsaicin. Coughs elicited by TRPA1 agonists were reduced by non-selective (camphor and gentamicin) and selective (HC-030031) TRPA1 antagonists, whereas they were unaffected by the TRPV1 antagonist, capsazepine. Acrolein and crotonaldehyde, two alpha,beta-unsaturated aldehydes recently identified as TRPA1 stimulants and contained in cigarette smoke, air pollution or produced endogenously by oxidative stress, caused a remarkable tussive effect, a response that was selectively inhibited by HC-030031. Part of the cough response induced by cigarette smoke inhalation was inhibited by HC-030031, suggesting the involvement of TRPA1. CONCLUSIONS AND IMPLICATIONS: A novel pro-tussive pathway involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory nerves and is activated by a series of exogenous (cigarette smoke) and endogenous irritants. These results suggest TRPA1 may be a novel target for anti-tussive medicines.

Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk.

The functional consequences of missense variants are often difficult to predict. This becomes especially relevant when DNA sequence changes are used to determine a diagnosis or prognosis. To analyze the consequences of 12 missense variants in patients with mild forms of ataxia-telangiectasia (A-T), we employed site-directed mutagenesis of ataxia-telangiectasia mutated (ATM) cDNA followed by stable transfections into a single A-T cell line to isolate the effects of each allele on the cellular phenotype. After induction of the transfected cells with CdCl2, we monitored for successful ATM transcription and subsequently assessed: 1) intracellular ATM protein levels; 2) ionizing radiation (IR)-induced ATM kinase activity; and 3) cellular radiosensitivity. We then calculated SIFT and PolyPhen scores for the missense changes. Nine variants produced little or no correction of the A-T cellular phenotype and were interpreted to be ATM mutations; SIFT/PolyPhen scores supported this. Three variants corrected the cellular phenotype, suggesting that they represented benign variants or polymorphisms. SIFT and PolyPhen scores supported the functional analyses for one of these variants (c.1709T>C); the other two were predicted to be "not tolerated" (c.6188G>A and c.6325T>G) and were classified as "operationally neutral." Genotype/phenotype relationships were compared: three deleterious missense variants were associated with an increased risk of cancer (c.6679C>T, c.7271T>G, and c.8494C>T). In situ mutagenesis represents an effective experimental approach for distinguishing deleterious missense mutations from benign or operationally neutral missense variants.

Ataxia-oculomotor apraxia 2 patients show no increased sensitivity to ionizing radiation.

Mutations in senataxin have been described recently in 24 cases of French-Canadian descent with ataxia-oculomotor apraxia 2. This recessive ataxia is associated with an elevation in alpha-fetoprotein as in ataxia-telangiectasia. Because ataxia-telangiectasia cells are highly radiosensitive, we used a colony survival assay to measure the radiosensitivity of lymphoblastoid cell lines derived from five French-Canadian patients with ataxia-oculomotor apraxia 2. Two were homozygous for the common French-Canadian L1976R SETX missense mutation; the three others were compound heterozygotes for the common mutation and three different missense mutations. Overall, lymphoblastoid cell lines derived from these cases did not show significant variation from a normal response to 1 Gray of ionizing radiation but the two patients who were homozygous for the common L1976R mutation fell in the intermediate or non-diagnostic range.

Transcriptional response to ionizing radiation in human radiation sensitive cell lines.

BACKGROUND AND PURPOSE: Radiation is a common treatment of cancer, but some patients show severe side effects when exposed to small doses of radiation. The aim of this study was to explore the underlying cause of radiation sensitivity in a group of radiation sensitive patients. MATERIALS AND METHODS: Lymphoblastoid cell lines from 5 normal individuals, 4 Ataxia Telangiectasia (AT), and 12 non-AT radiation sensitive (RS) patients were irradiated. RNA was isolated before and after radiation and hybridized to 15k cDNA microarrays and gene expression was recorded. RESULTS AND CONCLUSION: The RS cell lines showed an expression phenotype different from both the AT and normal cell lines. Six of the RS cell lines had a distinct expression profile before radiation. This implies that the RS patients are a heterogeneous group, but that six of the patients may have a common cause of radiation sensitivity.

The inhibition of glutamine synthetase sensitizes human sarcoma cells to L-asparaginase.

PURPOSE: To evaluate the activity of the antitumor enzyme L: -asparaginase (ASNase) on tumor cells of mesenchymal origin and the contribution of glutamine synthetase (GS) to the adaptation to the metabolic stress caused by the anti-tumor enzyme. METHODS: We studied the effects of ASNase in six human sarcoma cell lines: HT1080 (fibrosarcoma); RD (rhabdomyosarcoma); SW872 (liposarcoma); HOS, SAOS-2, and U2OS (osteosarcoma) in the absence or in the presence of the GS inhibitor methionine L: -sulfoximine (MSO). RESULTS: HT1080 and SW872 cells were highly sensitive to ASNase-dependent cytotoxicity. In contrast, RD, SAOS-2, HOS, and U2OS cells exhibited only a partial growth suppression upon treatment with the anti-tumor enzyme. In these cell lines ASNase treatment was associated with increased levels of GS. When ASNase was used together with MSO, the proliferation of the poorly sensitive cell lines was completely blocked and a significant decrease in the IC(50) for ASNase was observed. Moreover, when ASNase treatment was carried on in the presence of MSO, HOS and U2OS osteosarcoma cells exhibited a marked cytotoxicity, with increased apoptosis. CONCLUSIONS: In human sarcoma cells (1) GS markedly contributes to the metabolic adaptation of tumor cells to ASNase and (2) the inhibition of GS activity enhances the antiproliferative and cytotoxic effects of ASNase. The two-step interference with glutamine metabolism, obtained through the combined treatment with ASNase and MSO, may provide a novel therapeutic approach that should be further investigated in human tumors of mesenchymal origin.

Non-apoptotic programmed cell death induced by a copper(II) complex in human fibrosarcoma cells.

A0, a Cu(II) thioxotriazole complex, produces severe cytotoxic effects on HT1080 human fibrosarcoma cells with a potency comparable to that exhibited by cisplatin. A0 induced a characteristic series of changes, hallmarked by the formation of eosin- and Sudan Black-B-negative vacuoles. No evidence of nuclear fragmentation or caspase-3 activation was detected in cells treated with A0 which, rather, inhibited cisplatin-stimulated caspase-3 activity. Membrane functional integrity, assessed with calcein and propidium iodide, was spared until the late stages of the death process induced by the copper complex. Vacuoles were negative to the autophagy marker monodansylcadaverine and their formation was not blocked by 3-methyladenine, an inhibitor of autophagic processes. Negativity to the extracellular marker pyranine excluded vacuole derivation from the extracellular fluid. Ultrastructural analysis indicated that A0 caused the appearance of many electronlight cytoplasmic vesicles, possibly related to the endoplasmic reticulum, which progressively enlarge and coalesce to form large vacuolar structures that eventually fill the cytoplasm. It is concluded that A0 triggers a non-apoptotic, type 3B programmed cell death (Clarke in Anat Embryol (Berl) 181:195-213, 1990), characterized by an extensive cytoplasmic vacuolization. This peculiar cytotoxicity pattern may render the employment of A0 to be of particular interest in apoptosis-resistant cell models.

ATM gene founder haplotypes and associated mutations in Polish families with ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is an early onset autosomal recessive ataxia associated with characteristic chromosomal aberrations, cell cycle checkpoint defects, cancer susceptibility, and sensitivity to ionizing radiation. We utilized the protein truncation test (PTT), and single strand conformation polymorphism (SSCP) on cDNA, as well as denaturing high performance liquid chromatography (dHPLC) on genomic DNA (gDNA) to screen for mutations in 24 Polish A-T families. Twenty-six distinct Short Tandem Repeat (STR) haplotypes were identified. Three founder mutations accounted for 58% of the alleles. Three-quarters of the families had at least one recurring (shared) mutation, which was somewhat surprising given the low frequency of consanguinity in Poland. STR haplotyping greatly improved the efficiency of mutation detection. We identified 44 of the expected 48 mutations (92%): sixty-nine percent were nonsense mutations, 23% caused aberrant splicing, and 5% were missense mutations. Four mutations have not been previously described. Two of the Polish mutations have been observed previously in Amish and Mennonite A-T patients; this is compatible with historical records. Shared mutations shared the same Single Nucleotide Polymorphism (SNP) and STR haplotypes, indicating common ancestries. The Mennonite mutation, 5932 G>T, is common in Russian A-T families, and the STR haplovariants are the same in both Poland and Russia. Attempts to correlate phenotypes with genotypes were inconclusive due to the limited numbers of patients with identical mutations.

Ethanol increases the paracellular permeability of monolayers of CAPAN-1 pancreatic duct cells.

When grown on permeable supports, pancreatic duct adenocarcinoma CAPAN-1 cells establish very high values of transepithelial resistance (TER). The addition of ethanol produced a dose-related, reversible drop in the TER of these cells, ranging from 15% (with 1% ethanol) to 65% (with 10% ethanol). The ethanol effect was rapid and reversible. The resistance decrease was associated with an increase in monolayer permeability to mannitol. No significant decrease in cell ATP was detected for ethanol concentrations lower than 7%. Confocal vertical sections of calcein-loaded monolayers of CAPAN-1 cells, grown on plasticware, showed a progressive deflation of domes detectable after 5 min of treatment with 2% ethanol. Incubation in an ethanol-free medium caused a progressive dome restoration. Immunocytochemical analysis of ethanol-treated cells indicated that ZO-1 and occludin exhibited clear cut distribution changes while the perijunctional actin pattern was slightly modified. Electron microscopy showed that a discrete intercellular space was detectable between adjacent ethanol-treated cells but not between control cells. These data indicate that ethanol is a tight junction barrier opener in pancreatic duct cells.

Antitussive activity of iodo-resiniferatoxin in guinea pigs.

BACKGROUND: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). METHODS: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. RESULTS: Pretreatment with I-RTX either intraperitoneally (0.03-0.3 micromol/kg) or by aerosol (0.1-3 microM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 microM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10-100 times more potent than CPZ in all the experimental conditions tested. CONCLUSIONS: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation.

Pesticides re-entry dermal exposure of workers in greenhouses.

This research has the aim to evaluate the risk of pesticide dermal exposure for workers in greenhouses. We considered the following crops: tomato, cucumber and strawberry, largely spread in Bracciano lake district. The pesticides monitored were: tetradifon on strawberry: metalaxyl, azoxystrobin and fenarimol on cucumber; acrinathrin, azoxystrobin and chlorpyrifos ethyl on tomato. The dermal exposure was evaluated by Dislodgeable Foliar Residue (DFR) measurements employing transfer coefficients got from literature. For risk evaluation, we have compared the dermal exposures with Acceptable Operator Exposure Levels (AOEL). The re-entry time were obtained intercepting the dose decay curves with AOEL values. The re-entry times result higher than two days in the cases of chlorpyrifos on tomato (re-entry time: 3 days), azoxystrobin on tomato (4 days), and tetradifon on strawberry (8 days). The need of measuring specific transfer coefficients is pointed out.